Neurons whose primary neurotransmitter is DOPAMINE.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the PONS and the DIENCEPHALON. Midbrain contains two major parts, the dorsal TECTUM MESENCEPHALI and the ventral TEGMENTUM MESENCEPHALI, housing components of auditory, visual, and other sensorimoter systems.
The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)
A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.
A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.
A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.
Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.
Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.
A condition caused by the neurotoxin MPTP which causes selective destruction of nigrostriatal dopaminergic neurons. Clinical features include irreversible parkinsonian signs including rigidity and bradykinesia (PARKINSON DISEASE, SECONDARY). MPTP toxicity is also used as an animal model for the study of PARKINSON DISEASE. (Adams et al., Principles of Neurology, 6th ed, p1072; Neurology 1986 Feb;36(2):250-8)
An active neurotoxic metabolite of 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to PARAQUAT, has also been used as an herbicide.
Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.
A region in the MESENCEPHALON which is dorsomedial to the SUBSTANTIA NIGRA and ventral to the RED NUCLEUS. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the NUCLEUS ACCUMBENS. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of SCHIZOPHRENIA.
An orphan nuclear receptor that is found at high levels in BRAIN tissue. The protein is believed to play a role in development and maintenance of NEURONS, particularly dopaminergic neurons.
Neurons which activate MUSCLE CELLS.
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.
Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.
Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.
Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.
Drugs that bind to and activate dopamine receptors.
The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.
A deaminated metabolite of LEVODOPA.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A botanical insecticide that is an inhibitor of mitochondrial electron transport.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.
Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.
A family of vesicular amine transporter proteins that catalyze the transport and storage of CATECHOLAMINES and indolamines into SECRETORY VESICLES.
The most common inhibitory neurotransmitter in the central nervous system.
The observable response an animal makes to any situation.
The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.
A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.
Neurons whose primary neurotransmitter is GAMMA-AMINOBUTYRIC ACID.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
A poisonous dipyridilium compound used as contact herbicide. Contact with concentrated solutions causes irritation of the skin, cracking and shedding of the nails, and delayed healing of cuts and wounds.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)
Portion of midbrain situated under the dorsal TECTUM MESENCEPHALI. The two ventrolateral cylindrical masses or peduncles are large nerve fiber bundles providing a tract of passage between the FOREBRAIN with the HINDBRAIN. Ventral MIDBRAIN also contains three colorful structures: the GRAY MATTER (PERIAQUEDUCTAL GRAY), the black substance (SUBSTANTIA NIGRA), and the RED NUCLEUS.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
The paired caudal parts of the PROSENCEPHALON from which the THALAMUS; HYPOTHALAMUS; EPITHALAMUS; and SUBTHALAMUS are derived.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
A dopamine D2/D3 receptor agonist.
Refers to animals in the period of time just after birth.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists.
A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.
Neurons whose primary neurotransmitter is ACETYLCHOLINE.
Use of electric potential or currents to elicit biological responses.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.
Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Elements of limited time intervals, contributing to particular results or situations.
Compounds with BENZENE fused to AZEPINES.
A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
The function of opposing or restraining the excitation of neurons or their target excitable cells.
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
The physical activity of a human or an animal as a behavioral phenomenon.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
Transference of brain tissue, either from a fetus or from a born individual, between individuals of the same species or between individuals of different species.
Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.
Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A selective D1 dopamine receptor agonist used primarily as a research tool.
Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.
A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.
Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.
Transference of fetal tissue between individuals of the same species or between individuals of different species.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.
The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.
An object or a situation that can serve to reinforce a response, to satisfy a motive, or to afford pleasure.
Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
The largest and most lateral of the BASAL GANGLIA lying between the lateral medullary lamina of the GLOBUS PALLIDUS and the EXTERNAL CAPSULE. It is part of the neostriatum and forms part of the LENTIFORM NUCLEUS along with the GLOBUS PALLIDUS.
Mice which carry mutant genes for neurologic defects or abnormalities.
The anterior of the three primitive cerebral vesicles of the embryonic brain arising from the NEURAL TUBE. It subdivides to form DIENCEPHALON and TELENCEPHALON. (Stedmans Medical Dictionary, 27th ed)
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.
Drugs that inhibit the actions of the sympathetic nervous system by any mechanism. The most common of these are the ADRENERGIC ANTAGONISTS and drugs that deplete norepinephrine or reduce the release of transmitters from adrenergic postganglionic terminals (see ADRENERGIC AGENTS). Drugs that act in the central nervous system to reduce sympathetic activity (e.g., centrally acting alpha-2 adrenergic agonists, see ADRENERGIC ALPHA-AGONISTS) are included here.
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.
Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain.
A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.
Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.
Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.
Calcium-binding proteins that are found in DISTAL KIDNEY TUBULES, INTESTINES, BRAIN, and other tissues where they bind, buffer and transport cytoplasmic calcium. Calbindins possess a variable number of EF-HAND MOTIFS which contain calcium-binding sites. Some isoforms are regulated by VITAMIN D.
Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.
In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.
Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive.
A complex group of fibers arising from the basal olfactory regions, the periamygdaloid region, and the septal nuclei, and passing to the lateral hypothalamus. Some fibers continue into the tegmentum.
A calbindin protein found in many mammalian tissues, including the UTERUS, PLACENTA, BONE, PITUITARY GLAND, and KIDNEYS. In intestinal ENTEROCYTES it mediates intracellular calcium transport from apical to basolateral membranes via calcium binding at two EF-HAND MOTIFS. Expression is regulated in some tissues by VITAMIN D.
Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.
Ovoid body resting on the CRIBRIFORM PLATE of the ethmoid bone where the OLFACTORY NERVE terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose DENDRITES the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the VOMERONASAL ORGAN via the vomeronasal nerve, is also included here.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.
A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994)
An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.
A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
Neurons in the OLFACTORY EPITHELIUM with proteins (RECEPTORS, ODORANT) that bind, and thus detect, odorants. These neurons send their DENDRITES to the surface of the epithelium with the odorant receptors residing in the apical non-motile cilia. Their unmyelinated AXONS synapse in the OLFACTORY BULB of the BRAIN.
Prominent lobed neuropils found in ANNELIDA and all ARTHROPODS except crustaceans. They are thought to be involved in olfactory learning and memory.
Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.
A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.
Dopamines with a hydroxy group substituted in one or more positions.
Manganese derivative of ethylenebisdithiocarbamate. It is used in agriculture as a fungicide and has been shown to cause irritation to the eyes, nose, skin, and throat.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
The electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electrical charges.
A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the AMYGDALA; EPITHALAMUS; GYRUS CINGULI; hippocampal formation (see HIPPOCAMPUS); HYPOTHALAMUS; PARAHIPPOCAMPAL GYRUS; SEPTAL NUCLEI; anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)).
A subclass of LIM domain proteins that include an additional centrally-located homeodomain region that binds AT-rich sites on DNA. Many LIM-homeodomain proteins play a role as transcriptional regulators that direct cell fate.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.
An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.
An inhibitor of the enzyme TYROSINE 3-MONOOXYGENASE, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with PHEOCHROMOCYTOMA. (Martindale, The Extra Pharmacopoeia, 30th ed)
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Paired bodies containing mostly GRAY MATTER and forming part of the lateral wall of the THIRD VENTRICLE of the brain.
Bluish-colored region in the superior angle of the FOURTH VENTRICLE floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the PERIAQUEDUCTAL GRAY.
A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.
Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms.
Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Neurons which send impulses peripherally to activate muscles or secretory cells.
The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)
Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region.
A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The act of injuring one's own body to the extent of cutting off or permanently destroying a limb or other essential part of a body.
Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.
Neurons whose primary neurotransmitter is SEROTONIN.
A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor (see RECEPTORS, DOPAMINE D2) antagonist.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.
Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ION EXCHANGE; AIR IONIZATION nor PHONOPHORESIS, none of which requires current.
A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)
Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.
Neural tracts connecting one part of the nervous system with another.
Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.
A series of structurally-related alkaloids that contain the ergoline backbone structure.
An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.
The time from the onset of a stimulus until a response is observed.
N-methyl-8-azabicyclo[3.2.1]octanes best known for the ones found in PLANTS.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.
The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.
The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin.
A c-jun amino-terminal kinase that is found predominantly within NEURONS of the BRAIN, suggesting a role in stress-induced neuronal APOPTOSIS. Several isoforms of the protein with molecular sizes of 47 kDa and 52 kDa exist due to multiple ALTERNATIVE SPLICING.
Heterocyclic acids that are derivatives of 4-pyridinecarboxylic acid (isonicotinic acid).
The lower portion of the BRAIN STEM. It is inferior to the PONS and anterior to the CEREBELLUM. Medulla oblongata serves as a relay station between the brain and the spinal cord, and contains centers for regulating respiratory, vasomotor, cardiac, and reflex activities.
A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.
The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus.
A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction.
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
The front part of the hindbrain (RHOMBENCEPHALON) that lies between the MEDULLA and the midbrain (MESENCEPHALON) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the CEREBELLUM to the CEREBRUM.
Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).
Subcellular structures found in nerve cell bodies and DENDRITES. They consist of granular endoplasmic reticulum (ENDOPLASMIC RETICULUM, ROUGH) and RIBOSOMES.
Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.

Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway. (1/670)

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Comparison of the temporal programs regulating tyrosine hydroxylase and enkephalin expressions in TIDA neurons of lactating rats following pup removal and then pup return. (2/670)

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Enhanced dopamine transporter activity in middle-aged Gdnf heterozygous mice. (3/670)

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Differential glutamate AMPA-receptor plasticity in subpopulations of VTA neurons in the presence or absence of residual cocaine: implications for the development of addiction. (4/670)

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Enhanced survival of dopaminergic neuronal transplants in hemiparkinsonian rats by the p53 inactivator PFT-alpha. (5/670)

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Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations. (6/670)

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Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis. (7/670)

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JNK isoforms differentially regulate neurite growth and regeneration in dopaminergic neurons in vitro. (8/670)

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Disclosed herein are methods for generating dopaminergic neurons in vitro by inhibiting a pathway component of a TGF-β signaling pathway and overexpressing one or more cell fate-inducing polypeptides in pluripotent cells, causing differentiation of the pluripotent cells into dopaminergic neurons. Also disclosed are methods for treating a neurodegenerative disease in a patient by generating dopaminergic neurons in vitro, and transplanting them into the brain of the patient, such that the dopaminergic neurons are sufficient to reduce or eliminate the symptoms of the neurodegenerative disease.
Parkinsons disease (PD) is a devastating movement disorder caused by the death of dopaminergic neurons (a type of nerve cells in the central nervous system) present in the midbrain. These neurons secrete dopamine (a signaling molecule) and are a critical component of the motor circuit that ensures movements are smooth and coordinated. All current treatments attempt to overcome the loss of these neurons by either replacing the lost dopamine, or modulating other parts of the circuit to balance this loss or attempting to halt or delay the loss of dopaminergic neurons. Cell replacement therapy (that is, transplantation of dopaminergic neurons into the brain to replace lost cells and restore function) as proposed in this application attempts to use cells as small pumps of dopamine that will be secreted locally and in a regulated way, and will therefore avoid the complications of other modes of treatment. Indeed, cell therapy using fetal tissue-derived cells have been shown to be successful in ...
A new study has shown the link between noradrenergic neurons and susceptibility to depression for the first time. The study was published by Bruno Giros team, a researcher at the Douglas Mental Health University Institute and Professor of psychiatry at McGill University, in the journal Nature Neuroscience. We know that a small cerebral structure, known as the ventral tegmental area, contains dopaminergic neurons that play a key role in vulnerability to depression, said Bruno Giros, whose team is part of the CIUSSS de lOuest-de-lÎle-de-Montréal research network. By mimicking stressful events in animal models, the researchers found out that an increase in dopaminergic activity increases cases of depression. The dopaminergic neuron is controlled by the noradrenergic neuron. It is this control that steers the bodys response toward resilience or toward vulnerability to depression, said Giros. Giros team showed, animals incapable of releasing noradrenaline, are more likely to develop ...
Loss of dopaminergic neurons is seen in Parkinson s disease, and transplantation of these neurons can greatly ease symptoms. However, several major drawbacks are associated with transplantation-based therapy, begging for alternatives to treat Parkinson s. Cutting-edge research shows that the fate of cells can be re-engineered in the adult brain, raising the hope of using a patient s own cells for therapy rather than transplantation. Hypothesis ...
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TY - JOUR. T1 - Caspase-dependent and -independent cell death pathways in primary cultures of mesencephalic dopaminergic neurons after neurotoxin treatment. AU - Han, Baek S.. AU - Hong, Hyun Seung. AU - Choi, Won Seok. AU - Markelonis, George J.. AU - Oh, Tae H.. AU - Oh, Young Jun. PY - 2003/6/15. Y1 - 2003/6/15. N2 - Although the cause of neuronal death in Parkinsons disease (PD) is mainly unknown, growing evidence suggests that both apoptotic and non-apoptotic death may occur in PD. Using primary cultures of mesencephalic dopaminergic neurons and the MN9D dopaminergic neuronal cell line, we attempted to evaluate specifically the existence of the mitochondrial apoptotic pathway, focusing on the mitochondrial release of cytochrome c to the activation of the caspases after 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+) treatment. Both immunofluorescent labeling and immunoblot analysis indicated mitochondrial release of cytochrome c into the cytosol after 6-OHDA or MPP+ ...
During the initial phases of nervous system development, progenitor cells in the neural tube proliferate and divide symmetrically to give rise to identical multipotent neuroepithelial cells. These progenitors subsequently divide asymmetrically to generate cells that are fated to differentiate into a neuron, sometimes following additional cycles of cell division. This process is regulated by the activity of transcription factors with basic helix-loop-helix (bHLH) motifs, including the neurogenin and Mash1 proneural factors involved in initiating neurogenesis, and other bHLH factors, such as Neurod, that are involved in terminal neuronal differentiation.. The proneural genes of the bHLH class were first identified in Drosophila as key regulators of neural lineage development (Brunet and Ghysen, 1999; Guillemot, 1999). The three most extensively studied genes in rodents are the mouse achaete-scute homologue (Mash1) and the members of the atonal-related family of genes, neurogenins (Ngn) 1 and 2 ...
TY - JOUR. T1 - Degeneration of dopaminergic neurons in the substantia nigra of zitter mutant rat and protection by chronic intake of Vitamin E. AU - Ueda, Shuichi. AU - Sakakibara, Shin Ichi. AU - Nakadate, Kazuhiko. AU - Noda, Takahiro. AU - Shinoda, Motoo. AU - Joyce, Jeffrey N.. PY - 2005/6/3. Y1 - 2005/6/3. N2 - Dopaminergic cell death in the ventral and dorsal tiers of substantia nigra pars copmacta (SNc) and their prevention by anti-oxidant diet was immunohistochemically studied in the zitter mutant rats, which are characterized by abnormal metabolism of superoxide. Similar to previous reports, the number of SNc neurons in Nissl-stained section decreased with age. Tyrosine hydroxylase (TH) immunohistochemistry demonstrated that the dopaminergic neurons in the ventral tier of SNc degenerated early, whereas the dorsal tier gradually degenerated with age. Thus, the ventral tier dopaminergic neurons are affected first, but the dorsal tier neurons do become impact by the zi/zi mutation. ...
Neurons that produce dopamine as a neurotransmitter constitute a heterogeneous group involved in the control of various behaviors and physiology. In mammals, dopaminergic neurons are found in distinct clusters mainly located in the ventral midbrain and the caudal forebrain [1]. Although much is known about midbrain dopaminergic neurons, development of diencephalic dopaminergic neurons is poorly understood. Here we demonstrate that Orthopedia (Otp) homeodomain protein is essential for the development of specific subsets of diencephalic dopaminergic neurons. Zebrafish embryos lacking Otp activity are devoid of dopaminergic neurons in the hypothalamus and the posterior tuberculum. Similarly, Otp(-/-) mouse [2, 3] embryos lack diencephalic dopaminergic neurons of the A11 group, which constitutes the diencephalospinal dopaminergic system. In both systems, Otp is expressed in the affected dopaminergic neurons as well as in potential precursor populations, and it might contribute to dopaminergic cell ...
Midbrain dopaminergic neurons, whose loss in adults results in Parkinsons disease, can be specified during embryonic development by a contact-dependent signal from floor plate cells. Here we show that the amino-terminal product of Sonic hedgehog autoproteolysis (SHH-N), an inductive signal expresse …
Parkinsons Disease (PD) is a complex, chronic, progressive, and debilitating neurodegenerative disorder. Neither a cure nor effective long-term therapy exist and the lack of knowledge of the molecular mechanisms responsible for PD development is a major impediment to therapeutic advances. The protein alphaSynuclein is a central component in PD pathogenesis yet its cellular targets and mechanism of toxicity remains unknown. Mitochondrial dysfunction is also a common theme in PD patients and this review explores the strong possibility that alphaSynuclein and mitochondrial dysfunction have an inter-relationship responsible for underlying the disease pathology. Amplifying cycles of mitochondrial dysfunction and alphaSynuclein toxicity can be envisaged, with either being the disease-initiating factor yet acting together during disease progression. Multiple potential mechanisms exist in which mitochondrial dysfunction and alphaSynuclein could interact to exacerbate their neurodegenerative properties.
The cardinal motor symptoms of Parkinsons disease (PD) are caused by the vulnerability to dysfunction and degeneration of ventral midbrain (VM) dopaminergic (DA) neurons. A major limitation for experimental studies of current ES/iPS cell differentiation protocols is the lack of VM DA neurons with a …
Understanding human embryonic ventral midbrain is of major interest for Parkinsons disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like cells and four progenitors. In the mouse, two mature fetal dopaminergic neuron subtypes diversified into five adult classes during postnatal development. Cell types and gene expression were generally conserved across species, but with clear differences in cell proliferation, developmental timing, and dopaminergic neuron development. Additionally, we developed a method to quantitatively assess the fidelity of dopaminergic neurons derived from human pluripotent stem cells, at a single-cell level. Thus, our study provides insight into the molecular programs controlling human midbrain
Dopaminergic (DA) neurons display two functionally distinct modes of electrical activity: low- and high-frequency firing. We suggest a new minimal computational model that unites data on these firing modes obtained under different experimental conditions. The model reproduces the separation of maximal frequencies under NMDA synaptic stimulation vs. other treatments. In accord to recent experimental data, NMDA stimulation restricted to the soma effectively evokes high-frequency oscillations in the model. We have also reproduced low- and high-frequency oscillations under blockade of the SK current. Thus, the new model suggests a way that overcomes all major limitations of the switching dominance mechanism for controlling the frequency of the DA neuron. We explain recent experimental facts and make further predictions. ...
Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is widely used as a broad-spectrum herbicide. Animal studies have demonstrated that ATR exposure can cause cell death in dopaminergic neurons. The molecular mechanisms underlying ATR-induced neuronal cell death, however, are unknown. In this study, we investigated the autophagy and apoptosis induced by ATR in dopaminergic neurons in vivo. Wistar rats were administered with ATR at doses of 10, 50 and 100 mg/kg body weight by oral gavage for three months. In terms of histopathology, the expression of autophagy- and apoptosis-related genes as well as proteins related to the Beclin-1/B-cell lymphoma 2 (Bcl-2) autophagy and apoptosis pathways were examined in the rat nigrostriatal dopaminergic system. We observed degenerative micromorphology indicative of neuronal apoptosis and mitochondrial autophagy by electron microscopy in ATR-exposed rat striatum. The rat ventral mesencephalon in the ATR-exposed groups also showed increased
CNM-Au8, an investigational therapy by Clene Nanomedicine, improved the survival of dopaminergic neurons, helped prevent loss of mitochondria, and rescued motor function in a rat model of Parkinsons disease, a study reports.. The effects of CNM-Au8 will now be assessed in an open-label (no placebo group) Phase 2 trial, called REPAIR-PD (NCT03815916). This pilot study is enrolling up to 24 patients who will undergo treatment at the University of Texas Southwestern Medical Center. More information can be found here.. Karen Ho, Clenes head of translational medicine, presented the preclinical findings in the scientific poster, Gold nanocatalysis as a novel therapeutic for neuroprotection in Parkinsons disease, during the recent 2019 Society for Neuroscience (SfN) Annual Meeting in Chicago.. Parkinsons disease is characterized by the degeneration and death of a particular group of nerve cells - called dopaminergic neurons - in two brain regions, the striatum and the substantia nigra.. To work ...
Parkinson¿s disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurones. Donor fetal tissue transplantation showed promise in addressing some of the symptoms of PD. Derivation of dopaminergic cells from human embryonic stem cells (hESCs) could provide new options for PD therapy. Dopaminergic cells are derived from SOX- floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to effectively convert hESCs into FP fates. Due to the complex origin of FP cells, we hypothesized a SHH free approach in deriving SOX1- FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved under dual inhibition of BMP4 (LDN193189) and TGF-ß pathways (SB431542) under minimal condition. Followed by 5 days inhibition with LDN or LDN+SB±PD173074(FGF2 inhibitor), SOX1- FP cells accounts to 70-80% of the whole population. When patterned with SHH and FGF8, the ...
This disclosure provides improved methods for obtaining populations of neural progenitor cells and differentiated neurons from pluripotent stem cells. The technology can be used to produce progenitors that proliferate through at least 40 doublings, while maintaining the ability to differentiate into a variety of different neural phenotypes. Cell populations have been obtained that contain a high proportion of cells staining for tyrosine hydroxylase, which is a feature of dopaminergic neurons. The neural progenitors and terminally differentiated neurons of this invention can be generated in large quantities for use in drug screening and the treatment of clinically important neurological disorders, such as Parkinsons disease ...
TY - GEN. T1 - Scalable production of dopaminergic neuron progenitors for treating parkinsons disease. AU - Lei, Y.. AU - Schaffer, D.. PY - 2013. Y1 - 2013. UR - http://www.scopus.com/inward/record.url?scp=84911444592&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84911444592&partnerID=8YFLogxK. M3 - Conference contribution. AN - SCOPUS:84911444592. T3 - Food, Pharmaceutical and Bioengineering Division 2013 - Core Programming Area at the 2013 AIChE Annual Meeting: Global Challenges for Engineering a Sustainable Future. SP - 316. BT - Food, Pharmaceutical and Bioengineering Division 2013 - Core Programming Area at the 2013 AIChE Annual Meeting. PB - AIChE. T2 - Food, Pharmaceutical and Bioengineering Division 2013 - Core Programming Area at the 2013 AIChE Annual Meeting: Global Challenges for Engineering a Sustainable Future. Y2 - 3 November 2013 through 8 November 2013. ER - ...
Computational modeling showed that the size of the Axon Initial Segment (AIS), but not its position within the somatodendritic domain, is the major causal determinant of the tonic firing rate in the intact model, by virtue of the higher intrinsic frequency of the isolated AIS. Further mechanistic analysis of the relationship between neuronal morphology and firing rate showed that dopaminergic neurons function as a coupled oscillator whose frequency of discharge results from a compromise between AIS and somatodendritic oscillators ...
Fingerprint Dive into the research topics of The dopaminergic neurons of the A11 system in RLS autopsy brains appear normal. Together they form a unique fingerprint. ...
Parkinsons disease is a progressive degenerative disorder of the nervous system that affects movement and motor function. Some common symptoms of the disease are tremors and difficulty walking, caused by degeneration of neurons that produce dopamine (also know as dopaminergic neurons).. In a recent study, Takuya Hayashi headed a team of researchers at the RIKEN Center for Molecular Imaging Science with the goal of regenerating dopaminergic neurons using autologus stem cells (or stem cells derived from a patients own body). The researchers directed the stem cells to differentiate into dopaminergic neurons in an animal model; monkeys suffering from Parkinsons disease.. Continue reading →. ...
J:107647 Thuret S, Bhatt L, OLeary DD, Simon HH, Identification and developmental analysis of genes expressed by dopaminergic neurons of the substantia nigra pars compacta. Mol Cell Neurosci. 2004 Mar;25(3):394-405 ...
Neural stem cells (NSCs) lose their competency to generate region-specific neuronal populations at an early stage during embryonic brain development. Here we investigated whether epigenetic modifications can reverse the regional restriction of mouse adult brain subventricular zone (SVZ) NSCs. Using a variety of chemicals that interfere with DNA methylation and histone acetylation, we showed that such epigenetic modifications increased neuronal differentiation but did not enable specific regional patterning, such as midbrain dopaminergic (DA) neuron generation. Only after Oct-4 overexpression did adult NSCs acquire a pluripotent state that allowed differentiation into midbrain DA neurons. DA neurons derived from Oct4-reprogrammed NSCs improved behavioural motor deficits in a rat model of Parkinsons disease (PD) upon intrastriatal transplantation. Here we report for the first time the successful differentiation of SVZ adult NSCs into functional region-specific midbrain DA neurons, by means of ...
The initial strategies for generation of DA neurons from hESCs were based on previous experience with mouse ESCs, which commonly used the developmental cues known at the time (Kawasaki et al., 2000; Kim et al., 2002). Several of these early differentiation protocols did indeed produce a relatively high number of cells expressing tyrosine hydroxylase (TH, the rate-limiting enzyme in dopamine synthesis and most commonly used marker for DA neurons), yet the midbrain properties of these neurons were not clear and their in vivo performance after grafting in standard animal models of PD was modest. A breakthrough in optimization of the differentiation protocols came when our understanding of how midbrain DA neurons are formed during normal development radically changed. In 2007 and 2008, two ground-breaking studies were published, both reporting that midbrain DA neurons were not derived from neuroepithelial cells (like all other neurons) but were in fact derived from floor-plate cells expressing ...
Abstract: Endocannabinoids as well as their receptors play a modulatory role from the control of dopamine transmission during the basal ganglia. On the other hand, this influence is usually indirect and exerted from the modulation of GABA and glutamate inputs obtained by nigrostriatal dopaminergic neurons, which lack cannabinoid CB1 receptors Even though They might produce endocannabinoids. Added proof implies that CB2 receptors could be situated in nigrostriatal dopaminergic neurons, and that particular eicosanoid-related cannabinoids may possibly straight activate TRPV1 receptors, that have been found in nigrostriatal dopaminergic neurons, As Find Out More a try this result making it possible for in both cases a immediate regulation of dopamine transmission by unique cannabinoids. Furthermore, CB1 receptors type heteromers with dopaminergic receptors which give Yet another pathway to immediate interactions between equally methods, in this case within the postsynaptic amount ...
Genetically engineered neural stem cell (NSC) lines are promising vectors for the treatment of neurodegenerative diseases, particularly Parkinsons disease (PD). Neurturin (NTN), a member of the glial cell line-derived neurotrophic factor (GDNF) family, has been demonstrated to act specifically on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for PD. In our previous work, we demonstrated that NTN-overexpressing c17.2 NSCs exerted dopaminergic neuroprotection in a rat model of PD. In this study, we transplanted NTN-c17.2 into the striatum of the 6-hydroxydopamine (6-OHDA) PD model to further determine the regenerative effect of NTN-c17.2 on the rat models of PD. After intrastriatal grafting, NTN-c17.2 cells differentiated and gradually downregulated nestin expression, while the grafts stably overexpressed NTN. Further, an observation of rotational behavior and the contents of neurotransmitters tested by high-performance liquid chromatography showed that the regenerative effect
Cypermethrin a class II pyrethroid pesticide is used to control insects in the household and CYC116 agricultural fields. research not only because of its variable responses depending upon the doses time Rabbit polyclonal to PLA2G12B. and routes of exposure and strain age gender and species of animals used across multiple studies but also due to its capability to induce the nigrostriatal dopaminergic neurodegeneration. This post describes the result of acute chronic adulthood and developmental exposures to cypermethrin in experimental animals. This article sheds light on cypermethrin-induced adjustments in the central anxious program including its contribution in the onset of particular features that are from the nigrostriatal dopaminergic neurodegeneration. Resemblances and dissimilarities of cypermethrin-induced nigrostriatal dopaminergic neurodegeneration with sporadic and chemicals-induced disease versions along using its advantages and pitfalls may also be discussed. ramifications of ...
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Rabbit Polyclonal to OR10J5 adherent monolayer tradition solution to examine variations in effectiveness of neural differentiation, PKO and WT Sera cells were differentiated into neurons from the adherent monolayer tradition technique. Morphological changes had been observed 20350-15-6 manufacture throughout a differentiation period, and immunocytochemistry was performed with MAP2, an adult neuron marker. There have been no variations in the morphology or differentiation of MAP2-positive cells between WT and PKO cells (Fig. 1A). Particularly, the effectiveness of neural differentiation into dopaminergic neurons demonstrated no difference between PKO and WT Sera cells, as dependant on immunocytochemistry with TH, a dopaminergic neuron marker (Fig. 1B). Real-time RT-PCR evaluation with dopaminergic neuron markers such as for example Nurr1, Pitx3, AADC, TH, and D2R also demonstrated no difference between WT and PKO cells (Fig. 1C). Fig. 1 Induction of dopaminergic neurons from wild-type (WT) and ...
TY - JOUR. T1 - Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells. AU - Yoshizaki, Takahito. AU - Inaji, Motoki. AU - Kouike, Hiroko. AU - Shimazaki, Takuya. AU - Sawamoto, Kazunobu. AU - Ando, Kiyoshi. AU - Date, Isao. AU - Kobayashi, Kazuto. AU - Suhara, Tetsuya. AU - Uchiyama, Yasuo. AU - Okano, Hideyuki. N1 - Funding Information: We thank T. Nakano for the PA6 cells, H. Niwa for the EB3 ES cells and H.J. Okano for valuable discussion. This work was supported by a grant from the Ministry of Education, Science, Sports, Culture and Technology, a grant from CREST of the Japan Science and Technology Agency, and a grant-in-aid from the 21st Century COE Program of the Ministry of Education, Science and Culture to Keio University.. PY - 2004/6/3. Y1 - 2004/6/3. N2 - Embryonic stem (ES) cells differentiate into dopamine (DA)-producing neurons when co-cultured with PA6 stromal cells, but the resulting cultures contain a variety of unidentified cells. In ...
Sigma-Aldrich offers abstracts and full-text articles by [Qingshan Wang, Eun-Joo Shin, Xuan-Khanh Thi Nguyen, Quan Li, Jae-Hyung Bach, Guoying Bing, Won-Ki Kim, Hyoung-Chun Kim, Jau-Shyong Hong].
Looking for online definition of dopaminergic in the Medical Dictionary? dopaminergic explanation free. What is dopaminergic? Meaning of dopaminergic medical term. What does dopaminergic mean?
PD is a neurodegenerative disorder that results from DAergic neuronal death in the SNpc (Dauer and Przedborski, 2003), resulting in motor deficits as well as non-motor symptoms, such as mood dysregulation. DAergic neuron degeneration is more concentrated in the SNpc ventral tier than the SNpc dorsal tier and VTA, suggesting that SN and VTA DAergic neurons have different susceptibilities to degeneration in PD (Brichta and Greengard, 2014). Ventral SNpc DAergic neurons innervate not only the striatum (Cebrián and Prensa, 2010) but also the PFC (Björklund and Dunnett, 2007), which is implicated in PD with depression (Aarsland et al., 2011). Thus, the SNpc ventral tier may be implicated in both the motor and non-motor symptoms of PD. Approximately 45% of patients with PD experience depression (Burn, 2002; Chaudhuri and Schapira, 2009), and 50% have comorbid anxiety (Brown et al., 2011). Although the etiology of mood disorders in PD is unclear, dysfunctional monoaminergic neurotransmission is ...
Stahl, Katja; Rahmani, Soulmaz; Prydz, Agnete; Skauli, Nadia; MacAulay, Nanna; Mylonakou, Maria-Niki; Torp, Reidun; Skare, Øivind; Berg, Torill; Leergaard, Trygve Brauns; Paulsen, Ragnhild Elisabeth; Ottersen, Ole Petter & Amiry-Moghaddam, Mahmood (2018). Targeted deletion of the aquaglyceroporin AQP9 is protective in a mouse model of Parkinsons disease. PLOS ONE. ISSN 1932-6203. 13(3) . doi: 10.1371/journal.pone.0194896 Fulltekst i vitenarkiv. Vis sammendrag More than 90% of the cases of Parkinsons disease have unknown etiology. Gradual loss of dopaminergic neurons of substantia nigra is the main cause of morbidity in this disease. External factors such as environmental toxins are believed to play a role in the cell loss, although the cause of the selective vulnerability of dopaminergic neurons remains unknown. We have previously shown that aquaglyceroporin AQP9 is expressed in dopaminergic neurons and astrocytes of rodent brain. AQP9 is permeable to a broad spectrum of substrates including ...
Figure 6: An NR2B-Dependent Decrease in the Expression of trkB Receptors Precedes the Disappearance of Dopaminergic Cells in Substantia Nigra in a Rat Model of Presymptomatic Parkinsons Disease
Parkinsons disease is a neurodegenerative disorder that results from the degeneration of dopaminergic neurons in the central...
RET encodes a receptor tyrosine kinase that is essential for spermatogenesis, development of the sensory, sympathetic, parasympathetic, and enteric nervous systems and the kidneys, as well as for maintenance of adult midbrain dopaminergic neurons. RE
To systematically address the contribution of AIS, dendritic and somatic compartments to shaping the two-component action potentials (APs), we modeled APs of male mouse and rat dopaminergic neurons. A parsimonious two-domain model, with high (AIS) and lower (dendro-somatic) Na+ conductance, reproduced the notch in the temporal derivatives, but not in the extracellular APs, regardless of morphology. The notch was only revealed when somatic active currents were reduced, constraining the model to three domains. Thus, an initial AIS spike is followed by an actively generated spike by the axon-bearing dendrite (ABD), in turn followed mostly passively by the soma. Larger AISs and thinner ABD (but not soma-to-AIS distance) accentuate the AIS component ...
In people suffering from Parkinsons, errors of metabolism in dopaminergic neurons of substantia nigra play an important role in pathophysiology of the dis
Mesencephalic astrocyte-derived neurotrophic factor (179 aa, ~20 kDa) is encoded by the human MANF gene. This protein is involved in both the function and survival of dopaminergic neurons.
Mount MP, Lira A, Grimes D, Smith PD, Faucher S, Slack R, Anisman H, Hayley S, Park DS. Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons ...
PEA & The Case for Chocoholics. PEA influences a great number of neurotransmitter and hormonal systems. Noradrenergic, Dopaminergic and Acetylcholinergic
TY - JOUR. T1 - Cysteine oxidation and redox signaling in dopaminergic neurons physiology and in Parkinsons disease. AU - Milanese, Chiara. AU - Payán-Gómez, César. AU - Mastroberardino, Pier G.. PY - 2019/5/8. Y1 - 2019/5/8. N2 - Parkinsons disease (PD)is a neurological disorder affecting dopaminergic neurons in the nigrostriatal pathways of the brain. PD is a multifactorial disease and its causes should be sought in detrimental interactions between genes and environment. Since early mechanistic studies, excessive oxidation - or oxidative stress - emerged as a recurring and fundamental pathogenic mechanism, and consequently received significant attention. More recent evidence obtained at single-cell resolution, however, indicates that dopaminergic neurons in the substantia nigra display increased oxidation levels also in normal, physiological conditions; differently than pathological oxidation, the importance of this phenomenon is underappreciated. The nigrostriatal dopaminergic system is ...
Introduction. Parkinsons disease (PD) is the second most frequent neurodegenerative disease, after Alzheimer disease, and affects approximately 1% to 2% of adults aged over 60, or 5-6 million people worldwide.1-3 The degeneration of dopaminergic neurons of the substantia nigra pars compacta and of nerve fibres projecting to the striatum significantly reduces the levels of dopamine, a neurotransmitter essential for neural modulation. This causes motor dysfunction, bradykinesia, postural instability, rigidity, and tremor, which are typical of the disease, as well as such non-motor symptoms as sleep disorders, depression, and cognitive impairment.3-7 Damage to dopaminergic neurons may be mediated by a number of pathogenic mechanisms, including mitochondrial dysfunction, apoptosis, transition metal accumulation, oxidative stress, inflammation, and protein misfolding and aggregation. Recent studies have shown that oxidative stress is the mechanism most closely linked to an increase in reactive ...
i] Correa M., Salamone J.D. THE MYSTERIOUS MOTIVATIONAL FUNCTIONS OF MESOLIMBIC DOPAMINE Neuron 2012 Nov 8; 76(3): 470-485. (source). [ii] Treadway T.T. et. Al. Dopaminergic Mechanisms of Individual Differences in Human Effort-Based Decision-Making The Journal of Neuroscience, 2 May 2012, 32(18):6170-6176 (source). [iii] Qi J., Zhang S., Wang H.L., Wang H., de Jesus Aceves Buendia J., Hoffman A.F., Lupica C.R., Seal R.P., Morales M. A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons. Nature Communications. 2014 Nov 12;5:5390. (source). [iv] Berridge K.C., Robinson T.E. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Research; Brain Research Reviews. 1998 Dec;28(3):309-69. (source). [v] Testa B., Mayer J.M. (1 August 2003). Hydrolysis in Drug and Prodrug Metabolism. John Wiley & Sons. pp. 109-. ISBN 978-3-906390-25-3. (source). [vi] Peterson A.L., Gilman T.L., Banks M.L., Sprague J.E. ...
Nurr1, an orphan nuclear receptor, plays an essential role in the generation and maintenance of dopaminergic neurons in the brain. Rare mutations in Nurr1 are associated with familial Parkinsons disease, but the underlying basis for this relationship has not been established. Here, we demonstrate that Nurr1 unexpectedly functions to inhibit expression of pro-inflammatory neurotoxic mediators in both microglia and astrocytes. Reduced Nurr1 expression results in exaggerated inflammatory responses in microglia that are further amplified by astrocytes, leading to the production of factors that cause death of tyrosine hydroxylase-expressing neurons. Nurr1 exerts anti-inflammatory effects by docking to NF-kappaB-p65 on target inflammatory gene promoters in a signal-dependent manner. Subsequently, Nurr1 recruits the CoREST corepressor complex, resulting in clearance of NF-kappaB-p65 and transcriptional repression. These studies suggest that Nurr1 protects against loss of dopaminergic neurons in ...
In contrast, in neurons projecting to dopamine neurons, dendrites curved and coursed circuitously or turned inward toward the soma (Figure 6K). Furthermore, spines of inputs to GABAergic neurons were evenly. spaced and were of similar size. In contrast, inputs to dopamine neurons had uneven spines and varicosities, and their dendrites were irregular in contour (Figures 6D and 6H, inset). These results suggest that, whereas neurons projecting to GABAergic neurons are click here consistent with typical medium spiny neurons, neurons projecting to dopaminergic neurons have significantly different morphologies. We make two conclusions from these data: First, striatal neurons do project monosynaptically to dopamine neurons; and second, our technique is capable of revealing exquisite, cell-type-specific connectivity. Whereas SNc dopamine neurons receive the most input from the DS, VTA dopamine Buparlisib neurons receive the most input from the Acb (Figure 3). Although heterogeneity of the Acb was ...
Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) integrate complex inputs to encode multiple signals that influence motivated behaviors via diverse projections. Here, we combine axon-initiated viral transduction with rabies-mediated trans-synaptic tracing and Cre-based cell-type-specific targeting to systematically map input-output relationships of VTA-DA neurons. We found that VTA-DA (and VTA-GABA) neurons receive excitatory, inhibitory, and modulatory input from diverse sources. VTA-DA neurons projecting to different forebrain regions exhibit specific biases in their input selection. VTA-DA neurons projecting to lateral and medial nucleus accumbens innervate largely non-overlapping striatal targets, with the latter also sending extensive extra-striatal axon collaterals. Using electrophysiology and behavior, we validated new circuits identified in our tracing studies, including a previously unappreciated top-down reinforcing circuit from anterior cortex to lateral nucleus ...
Benedetto, Alexandre and Au, Catherine and Aschner, Michael (2009) Manganese-induced dopaminergic neurodegeneration:insights into mechanisms and genetics shared with Parkinsons disease. Chemical Reviews, 109 (10). pp. 4862-4884. ISSN 0009-2665 Full text not available from this repository ...
Vertebrate dopaminergic neurons develop in distinct neural territories to constitute one of the major neuromodulatory systems. We have identified a zebrafish mutation in the bHLH-PAS family member arnt2, based on a strong reduction in cell number of specific dopaminergic neuron groups in the hypothalamus and posterior tuberculum. Knockdown of sim1 causes a dopaminergic phenotype similar to arnt2 mutants, suggesting that Sim1 acts as a binding partner of Arnt2, similar to their role in hypothalamic neuroendocrine cell specification. sim1, arnt2 and otp are co-expressed in dopaminergic neurons, and combined overexpression of Sim1 and Otp leads to formation of supernumerary dopaminergic neurons in the ventral diencephalon. Arnt2, Sim1 and Otp thus are core components of a conserved transcriptional network, which specifies neuroendocrine as well as A11-related dopaminergic neurons in the fish hypothalamus and posterior tuberculum. Our data suggest a common evolutionary origin of specific ...
Parkinsons disease (PD) is a neurological disorder characterized by a progressive degeneration of dopaminergic neurons located in the substantia nigra pars compacta (SNc).1 Dopaminergic neurons of the SNc send their axons along the nigrostriatal pathway to the striatum, where dopamine (DA) acts to modulate post-synaptic signaling. The striatum comprises a heterogeneous population of neurons that receives input from a number of regions, including motor and sensory cortices, and under the influence of DA utilizes this information to guide motor behavior.
article{da2a79d8-c24f-41f2-9532-9e6ccf2c6f1e, abstract = {Death of transplanted dopaminergic neurons is induced both during preparation of donor tissue and after intrastriatal grafting. Oxidative stress is thought to be partly responsible for this cell death. In the present study we compared the effects of three lipid peroxidation inhibitors, the lazaroids Tirilazad mesylate, U-83836E and U-101033, on survival of embryonic mesencephalic neurons in different paradigms. The lazaroids were equally potent in preventing serum deprivation-induced death of cultured dopaminergic neurons. In a second set of experiments, mesencephalic suspensions were pretreated with lazaroids and cell survival was analyzed immediately after dissociation, after 2 or 24 h in culture or after intrastriatal transplantation. Lazaroid pretreatment failed to protect mesencephalic neurons in the in vitro paradigms and U-101033E did not protect grafted dopaminergic neurons in contrast to the neuroprotective effects previously ...
Mutations in XPR1, a gene encoding an inorganic phosphate exporter, have recently been identified in patients with primary familial brain calcification (PFBC). Using Sanger sequencing, we screened XPR1 in 18 unrelated patients with PFBC and no SLC20A2, PDGFB, or PDGFRB mutation. XPR1 variants were tested in an in vitro physiological complementation assay and patient blood cells were assessed ex vivo for phosphate export. We identified a novel c.260T , C, p.(Leu87Pro) XPR1 variant in a 41-year-old man complaining of micrographia and dysarthria and demonstrating mild parkinsonism, cerebellar ataxia and executive dysfunction. Brain (123)I-Ioflupane scintigraphy showed marked dopaminergic neuron loss. Peripheral blood cells from the patient exhibited decreased phosphate export. XPR1 in which we introduced the mutation was not detectable at the cell surface and did not lead to phosphate export. These results confirm that loss of XPR1-mediated phosphate export function causes PFBC, occurring in less ...
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Currently, medications are being used to alleviate symptoms of Parkinsons disease. However, there are no government-approved drugs that can inhibit dopaminergic neuronal cell death. Then, the research teams have found the possibility in licorice, the herb medicine.. Dr. Yun-Il Lee carried out joint research with Professor Joo-Ho Shin and Professor Yunjong Lee from Sungkyunkwan University School of Medicine to study candidate compounds for the treatment of Parkinsons disease. For example, the researchers have identified the mechanism that cortisol, a stress hormone, promotes dopaminergic neuronal activity by inducing parkin protein expression that inhibits dopamine neuronal cell death.. In this study, the research teams found the candidate drugs that induce the expression of RNF146 protein involved in the inhibition of neuronal cell death through high-speed mass screening method using the natural materials library of the Natural Medicine Bank of Korea Foundation.. As a result, the study has ...
HIV can induce marked and debilitating neurologic complications in infected children, often in spite of the use of Highly Active Antiretroviral Therapy. Clinical observations suggest a specific vulnerability of dopaminergic neurons, yet few studies have examined the possibility that these functional impairments may be associated with dopamine-specific pathology in pediatric patients. We utilized an in vivo model to 1) examine dopaminergic molecular alterations attributable to the effects of HIV infection in the CNS, 2) to determine if oxidative stress may contribute to the development of molecular dopaminergic alterations, and 3) to assess whether a neuroprotective attempt specific to oxidative stress associated with catecholaminergic activity may be mounted by the CNS. Periadolescent HIV-1 transgenic rats were confronted with a dopamine challenge, following which mesencephalic tissues were assayed to determine changes in the expression of biomarkers vital to dopamine neurotransmission. In assaying
Parkinsons disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain. However, causes and mechanisms of the development of this disorder are still not fully understood. At the same time, it is well known that dysfunction of the ubiquitin-proteasome protein degradation system (UPPDS) is one of the major mechanisms of the pathogenesis of PD. In this study we have investigated alterations in expression of Uchl3, Ubr7, Ube3c, Usp19, Usp39, Ube2k, Ube2d3, Ube2m, Ube2g1 genes, which are directly involved in the functioning of the UPPDS, using the real-time PCR in mice with the MPTP-induced pre-symptomatic and early symptomatic stages of PD ...
Models of Dopamine Systems: Implications in Human Diseases. The brains nigrostriatal dopamine pathway is critical for movement control and regulation. Dysfunction of dopamine transmission through this pathway is associated with Parkinsons disease. Dopamine transmission might be disturbed when a person is exposed to environmental risk factors and is affected by genetic predisposition. The processes constitute a complex system that operates at multiple time scales and organizational levels. The need to understand such complexity suggests the use of methods from systems biology that complement more traditional biological research and clinical experience. In the work presented here we have developed computational models that capture the dynamics of dopamine signal at different locations and levels. These models have been utilized to study dynamics of the dopamine system and generate hypotheses of mechanisms of pesticides. Eventually, the models are hoped to be useful in biomarker discovery, ...
Ryan M Drenan, Sharon R Grady, Paul Whiteaker, Tristan McClure-Begley, Sheri McKinney, Julie M Miwa, Sujata Bupp, Nathaniel Heintz, J Michael McIntosh, Merouane Bencherif, Michael J Marks, Henry A Lester
MiRNAs, a group of powerful modulator of gene expression, participate in multiple cellular processes under physiological and pathological conditions. Emerging evidence shows that Drosha, which controls the initial step in canonical miRNA biogenesis, is involved in modulating cell survival and death in models of several diseases. However, the role of Drosha in Parkinsons disease (PD) has not been well established. Here, we show that the level of Drosha decreases in 6-OHDA-induced cellular and animal models of PD. 6-OHDA induced a p38 MAPK-dependent phosphorylation of Drosha. This triggered Drosha degradation. Enhancing the level of Drosha protected the dopaminergic (DA) neurons from 6-OHDA-induced toxicity in both in vitro and in vivo models of PD and alleviated the motor deficits of PD mice. These findings reveal that Drosha plays a critical role in the survival of DA neurons and suggest that stress-induced destabilization of Drosha may be part of the pathological process in PD ...
Lead, Cell, Disease, Neurons, Administration, Affect, Affects, Animals, Cocaine, Domperidone, Dopamine, Brain, Dopaminergic Neurons, Glial Cell, Microspheres, Survival, Treatment, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-hydroxydopamine, 6-ohda
Tytuł projektu: Rozbudowa i przekształcenie bibliograficznej bazy danych AGRO w bazę bibliograficzno-abstraktową z wykorzystaniem oprogramowania YADDA. Nr umowy: POIG 02.03.02-00-031/09 (okres realizacji 2009-2013 ...
Chi Wang Ip is the author of this article in the Journal of Visualized Experiments: Stereological Estimation of Dopaminergic Neuron Number in the Mouse Substantia Nigra Using the Optical Fractionator and Standard Microscopy Equipment
The article is entitled:. Lysosomal perturbations in human dopaminergic neurons derived from induced pluripotent stem cells with PARK2 mutation.. https://doi.org/10.1038/s41598-020-67091-6. The work was done in, BrainStem partner, Morten Meyers lab ...
... "cholinergic-dopaminergic reward link". Le Moal M (2002). "Mesocorticolimbic Dopaminergic Neurons". In Davis KL, Charney D, ... neurons. Ghrelin-responsiveness of these neurons is both leptin- and insulin-sensitive. Ghrelin reduces the sensitivity of ... In addition to its function in energy homeostasis, ghrelin also activates the cholinergic-dopaminergic reward link in inputs to ... Ghrelin receptors are located on neurons in this circuit. Hypothalamic ghrelin signalling is required for reward from alcohol ...
Neuron. PMID 29983326 DOI: 10.1016/j.neuron.2018.06.014 Zhang SX, Rogulja D, Crickmore MA. Dopaminergic Circuitry Underlying ... "Dopaminergic Circuitry Underlying Mating Drive". Neuron. 91 (1): 168-181. doi:10.1016/j.neuron.2016.05.020. ISSN 0896-6273. ... The mechanisms with which the dopaminergic neurons stimulate and terminate copulatory behavior are distinct and the element of ... Following this study, Rogulja and her colleagues explored how dopaminergic signals onto P1 neurons determine courtship ...
Kotowski SJ, Hopf FW, Seif T, Bonci A, von Zastrow M (July 2011). "Endocytosis promotes rapid dopaminergic signaling". Neuron. ... doi:10.1016/j.neuron.2011.05.036. PMC 3417347. PMID 21791287. "Tissue expression of EHD3 - Summary - The Human Protein Atlas". ...
Bubser M, Fadel JR, Jackson LL, Meador-Woodruff JH, Jing D, Deutch AY (June 2005). "Dopaminergic regulation of orexin neurons ...
"Therapeutic-Grade Dopaminergic Neurons From Stem Cells?". February 12, 2019. "Michael J Fox Foundation Lorenz Studer". ... He successfully demonstrated that upon transplantation, these newly developed dopaminergic neurons can improve clinical ... of human pluripotent stem cells into neural and neural crest tissues and for the generation of functional dopaminergic neurons ... "Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson/'s disease." Nature 480, no. ...
... dopaminergic neurons (Ascl1, Brn2, Myt1l, Lmx1a, and FoxA2) or (Ascl1, Nurr1, and Lmx1a) Astrocytes → dopaminergic neurons ( ... "Efficient Conversion of Astrocytes to Functional Midbrain Dopaminergic Neurons Using a Single Polycistronic Vector". PLoS ONE. ... "Direct conversion of human fibroblasts to dopaminergic neurons". Proceedings of the National Academy of Sciences. 108 (25): ... "Efficient Conversion of Astrocytes to Functional Midbrain Dopaminergic Neurons Using a Single Polycistronic Vector". PLoS ONE. ...
"Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons". Front Syst Neurosci. 5: 56. doi:10.3389/ ...
"The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons". The ... "Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons". Front. Syst. Neurosci. 5: 56. doi:10.3389/ ... Neuron. 83 (2): 404-416. doi:10.1016/j.neuron.2014.05.043. PMC 4159050. PMID 25033183. AMPH also increases intracellular ... The dopaminergic mechanisms of each drug are believed to underlie the pleasurable feelings elicited by these substances. ...
Miyazaki I, Asanuma M (June 2008). "Dopaminergic neuron-specific oxidative stress caused by dopamine itself" (PDF). Acta Medica ... sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized ... "Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons". Front. Syst. Neurosci. 5: 56. doi:10.3389/ ... Neuron. 83 (2): 404-416. doi:10.1016/j.neuron.2014.05.043. PMC 4159050. PMID 25033183. AMPH also increases intracellular ...
Miyazaki I, Asanuma M (June 2008). "Dopaminergic neuron-specific oxidative stress caused by dopamine itself" (PDF). Acta Medica ... TAAR1 reduces the firing rate of dopamine neurons, preventing a hyper-dopaminergic state. Amphetamine is also a substrate for ... dopaminergic nerve terminals in the NAc synapse on CART-containing neurons (Koylu et al., 1999), hence providing the proximity ... sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized ...
... is neurotoxic to human midbrain dopaminergic neurons at high doses. Methamphetamine has been shown to have a ... σ Receptors are present on dopaminergic neurons and their activation stimulates dopamine synthesis and release [11-13]. σ-2 ... Methamphetamine is directly neurotoxic to dopaminergic neurons in both lab animals and humans. Excitotoxicity, oxidative stress ... "Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons". Front. Syst. Neurosci. 5: 56. doi:10.3389/ ...
"Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons". Front. Syst. Neurosci. 5: 56. doi:10.3389/ ... neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic ... Neuron. 83 (2): 404-416. doi:10.1016/j.neuron.2014.05.043. PMC 4159050. PMID 25033183. AMPH also increases intracellular ... Dopaminergic drugs appear to override a safety switch and allow athletes to use a reserve capacity that is 'off-limits' in a ...
This layer models midbrain dopamine neurons. They control the dopaminergic modulation of the basal ganglia.[citation needed] ... The PVLV system controls the dopaminergic modulation of the basal ganglia (BG). Thus, BG/PVLV form an actor-critic architecture ...
Smits SM, Smidt MP (2006). "The role of Pitx3 in survival of midbrain dopaminergic neurons". Journal of Neural Transmission. ... and the specification and terminal differentiation of mesencephalic dopamine neurons in the substantia nigra compacta that are ... "Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron ... "Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3". Development. 131 ...
... has been found to directly inhibit the firing of midbrain dopaminergic neurons in the ventral tegmental area and ... "Modafinil inhibits rat midbrain dopaminergic neurons through D2-like receptors". Neuropharmacology. 52 (2): 626-33. doi:10.1016 ... or at least via activation of the dopaminergic system. In support of modafinil acting as a dopaminergic agent, its wakefulness- ... Quisenberry AJ, Baker LE (December 2015). "Dopaminergic mediation of the discriminative stimulus functions of modafinil in rats ...
"Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning". Science. 324 (5930): 1080-4. doi:10.1126/ ... Zemelman BV, Lee GA, Ng M, Miesenböck G (January 2002). "Selective photostimulation of genetically chARGed neurons". Neuron. 33 ... Neuron. 50 (1): 23-33. doi:10.1016/j.neuron.2006.02.026. PMC 1459045. PMID 16600853. Lagali PS, Balya D, Awatramani GB, Münch ... Neuron. 50 (1): 23-33. doi:10.1016/j.neuron.2006.02.026. PMC 1459045. PMID 16600853. (Using channelrhodopsin potentially to ...
The LHb inhibits dopaminergic neurons, decreasing the release of dopamine. It was determined by several animal studies that ... "Nicotine Enhances Excitability of Medial Habenular Neurons via Facilitation of Neurokinin Signaling". Journal of Neuroscience. ... "Nicotine regulates activity of lateral habenula neurons via presynaptic and postsynaptic mechanisms". Scientific Reports. 6: ...
As the VTA is an area dense in dopaminergic neurons that project to many areas of the brain, this suggests that dopaminergic ... Lipopolysaccharide challenges also inhibit activity of histaminergic and dopaminergic neurons. Increased circulating levels of ... Dopaminergic drugs appear to override a safety switch and allow athletes to use a reserve capacity that is 'off-limits' in a ... In high-ambient temperatures, dopaminergic manipulations clearly improve performance. The distribution of the power output ...
"Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons". Proceedings of the National Academy ... It was during this time that McMahon discovered the basal retinal neurons of the molluscan eye were the clock neurons. From ... Under the mentorship of Gene Block, McMahon recorded from the basal retinal neurons (BRNs), a homogenous group of neurons that ... Light at night, on the other hand, when these neurons are inactive, stimulates them and causes them to fire action potentials. ...
Flames N, Hobert O (2009). "Gene regulatory logic of dopaminergic neuron differentiation". Nature. 458 (7240): 885-890. doi: ... have been shown to be important players in the specification and differentiation of dopaminergic neurons in both C. elegans and ...
However TGF-α treatment did not result in neurogenesis dopaminergic neurons. The EGF/TGF-α family has been shown to regulate ... In an animal model of Parkinson's disease where dopaminergic neurons have been damaged by 6-hydroxydopamine, infusion of TGF-α ... proliferation and migration of endogenous adult neural progenitor cells without differentiation into dopaminergic neurons". J. ...
Tritsch NX, Ding JB, Sabatini BL (2012). "Dopaminergic neurons inhibit striatal output through non-canonical release of GABA". ... VMAT2 is essential for enabling the release of neurotransmitters from the axon terminals of monoamine neurons into the synaptic ... In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, VMAT2 function is also necessary for the vesicular ... in monoamine neurons.[medical citation needed] Other VMAT2 inhibitors such as GZ-793A inhibit the reinforcing effects of ...
Specifically, it begins on the cerebral cortex sending projections to neurons in striatum. These neurons will inhibit the ... Strongly innervated by dopaminergic fibers from the ventral tegmental area (VTA). The projections of the basolateral nucleus to ... Any movement of the body is detected by the vestibular sensory neurons, and the sensory motor replies by counteracting the ... Through literature, they have found that primary motor cortex neurons may control skill acquisition and retention. One of the ...
April 2003). "Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice". Neuron. 38 (2): 291-303. ... "Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice". Neuron. 38 (2): 291-303. doi:10.1016/ ...
Dopaminergic neurons of this pathway release dopamine from axon terminals that synapse onto GABAergic medium spiny neurons ( ... MSNs), also known as spiny projection neurons (SPNs), located in the striatum. Degeneration of dopaminergic neurons in the SNc ... Nigrostriatal dopaminergic neurons exhibit tonic and phasic patterns of neuronal firing activity. This can lead to different ... A small number of SNc dorsal tier dopamine neurons also project directly to the cortex, although most of the dopaminergic ...
Cholinergic interneurons and dopaminergic neurons in the midbrain are largely unaffected. Treatment for Huntington's disease is ... The same dopaminergic pathway is also involved in psychosis. Glutamate has become a candidate for treatment focus because ... Additionally, damage to neurons in nociceptive pathways leads to neuropathic pain. Three families in northern Pakistan were ... Neuron, 2006. pp. 33-38 Dawson, TM; Dawson, VL.Molecular pathways of neurodegeneration in Parkinson's Disease. Science, 2003. ...
Secondly, dopaminergic neurons in the pars compacta contain less calbindin than other dopaminergic neurons. Calbindin is a ... In primates, dopaminergic neuron activity increases in the nigrostriatal pathway when a new stimulus is presented. Dopaminergic ... the death of dopaminergic neurons in the substantia nigra). MPTP, is a neurotoxin specific to dopaminergic cells in the brain, ... continues to activate dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic projections from the ventral ...
Parkinson's disease results from loss of dopaminergic neurons in the striatum. Furthermore, most effective antipsychotics block ... A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which ... D3 receptors are highly expressed on neurons in islands of Calleja and nucleus accumbens shell and lowly expressed in areas ... D1 receptors are found mainly on neurons in the nucleus accumbens as well as substantia nigra, striatum, amygdala, frontal ...
2011). "NMDA Receptors in Dopaminergic Neurons Are Crucial for Habit Learning". Neuron. 72 (6): 1055-1066. doi:10.1016/j.neuron ... Neuron. 71 (6): 995-1013. doi:10.1016/j.neuron.2011.07.026. PMC 3779648. PMID 21943598. Cre lines characterized by the JAX Cre ... doi:10.1016/j.neuron.2008.08.027. PMC 2955977. PMID 18957226. 'Eternal Sunshine' drug selectively erases memories by New ... Oct 2008). "Inducible and selective erasure of memories in the mouse brain via chemical-genetic manipulation". Neuron. 60 (2): ...
... most likely due to the destruction of dopaminergic neurons in the olfactory bulb. Methotrexate, administered in the treatment ... axons from the olfactory receptor neurons intermingle with dendrites from intrinsic olfactory bulb neurons: mitrial/tufted ... These receptors are bipolar neurons that connect to the glomerular layer of the olfactory bulb, traveling through the ... cells and dopaminergic periglomerular cells. From the olfactory bulb, mitral/tufted cells send axons via the lateral olfactory ...
Alcohol activates dopaminergic circuits in the midbrain that also regulate the brain's analyzation and recognition of the ... GABA produces its normal inhibitory effects on cell activity by reducing a neuron's firing rate. When a GABA molecule attaches ... This hyperpolarization decreases the likelihood that the membrane will send an action potential to neighboring neurons; the ... outcomes of an action.[13][14] It is not yet clear on exactly how alcohol effects these dopaminergic circuits. The following ...
Studies in mice and rats have found that retinoids, including isotretinoin, bind to dopaminergic receptors in the central ... it increases expression of 5-HT1A receptors in the pre-synaptic neuron, which inhibit serotonin secretion.[40] Isotretinoin ... may affect dopaminergic neurotransmission by disrupting the structure of dopamine receptors and decreasing dopaminergic ... The dopamine hypothesis of schizophrenia and psychosis suggests that an increase in dopaminergic stimulation or sensitivity in ...
... also increases spontaneous pacemaking frequency in substantia nigra pars compacta dopaminergic neurons[3] ... The Ki of AmmTX3 was found to be approximately 131 nM when tested on striatal neurons in cell culture.[1] AmmTX3 has a small ... While AmmTX3 nearly completely blocks the transient component of the A-type potassium current in cerebellar granular neurons at ...
Reductions of miR-133b correlated to decreased numbers of dopaminergic neurons in the midbrain of PD patients.[87] miR-132, ... Jankovic J, Chen S, Le WD (2005). "The role of Nurr1 in the development of dopaminergic neurons and Parkinson's disease". ... Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra by causes ... As SMN protein generally promotes the survival of motor neurons, mutations in SMN1 results in slow degeneration motor neurons ...
... and PEA and p-TA have been reported to depress GABAB receptor-mediated responses in dopaminergic neurons (22,23). Although PEA ... By oral route, phenylethylamine's half-life is 5-10 minutes;[10] endogenously produced PEA in catecholamine neurons has a half- ... TAAR1 activity appears to depress monoamine transport and limit dopaminergic and serotonergic neuronal firing rates via ... it reduces neuron firing rate and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT ...
... simultaneously releasing excitatory neurotransmitters onto motor neurons. Because the number and function of GABAB receptors ... dopaminergic agents. *dextromethorphan. *glutamine. *antioxidants. *Lamotrigine[18]. The GABA(B) receptor antagonist, SGS-742, ... is a critical finding since myelin is the electrical and insulating phospholipid layer that surrounds the axons of many neurons ...
The LD50 of annonacin to dopaminergic neurons is 0.018 uM, which when compared to other known neurotoxins is 100-fold more ... "The mitochondrial complex i inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy ...
In the brain, these include the A9 dopaminergic neurons in the substantia nigra, astrocytes in the cerebral cortex and ... Other cells that contain haemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, ... and beta-globin in mesencephalic dopaminergic neurons and glial cells". Proc. Natl. Acad. Sci. 106 (36): 15454-59. Bibcode: ... "A9 dopaminergic neurons may be at particular risk since in addition to their high mitochondrial activity they are under intense ...
Decreased dopaminergic activity in CNS. *Inhibition of central neuron excitation.. *N6-3-methoxyl-4-hydroxybenzyl adenine ...
Noradrenergic neurons are located in two major regions in the brain. These regions are locus coeruleus and lateral tegmental. ... TCAs do not block dopamine transport directly, but might facilitate dopaminergic effects indirectly by inhibiting dopamine ... Overall, inhibition of norepinephrine reuptake induced by TCAs, leads to decreased rates of neuron firing (mediated through α2 ... The α2 receptors include presynaptic autoreceptors which limit the neurophysiological activity of noradrenergic neurons in the ...
... it creates a model of Parkinson's disease in rats by targeting and destroying dopaminergic neurons in the nigrostriatal pathway ... "The non-motor and non-dopaminergic fratures of PD". Parkinson's Disease : Non-Motor and Non-Dopaminergic Features. Olanow, C. ... in many of the remaining neurons. This loss of neurons is accompanied by the death of astrocytes (star-shaped glial cells) and ... of the dopamine secreting neurons in the substantia nigra pars compacta by the end of life)[51] and the presence of Lewy bodies ...
Miyazaki I, Asanuma M (June 2008). "Dopaminergic neuron-specific oxidative stress caused by dopamine itself". Acta Med. Okayama ... Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, resulting in an ... resulting in multiple downstream effects such as increase in activity of dopaminergic neurons in the midbrain reward system, ... Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.. ...
"Neuron. 77 (4): 736-749. doi:10.1016/j.neuron.2012.12.032. PMC 3584418. PMID 23439125.. ... Compared to dopaminergic stimulants like methamphetamine, the NMDAR antagonist phencyclidine can produce a wider range of ... "Neuron. 65 (2): 178-190. doi:10.1016/j.neuron.2010.01.008. PMID 20152125. S2CID 12987037.. ... doi:10.1016/j.neuron.2014.03.030. PMID 24742457.. *^ Choi DW, Koh JY, Peters S (January 1988). "Pharmacology of glutamate ...
The pathophysiology of Parkinson's disease is death of dopaminergic neurons as a result of changes in biological activity in ...
... the serotonergic neurons originate from the raphe nuclei within the brainstem as well; the dopaminergic neurons originate in ... CB1 is present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons in the ... They excite the REM-off monoaminergic neurons during wakefulness and the PT cholinergic neurons during REM sleep. They are ... and the dopaminergic ventral tegmental area (VTA). ... Orexin neurons project to and activate monoaminergic and cholinergic ...
"Neuron. 83 (5): 1002-1018. doi:10.1016/j.neuron.2014.08.011. PMC 4156912. PMID 25175878.. ... Noradrenergic projections from the LC thus interact with dopaminergic projections from the VTA to regulate cognitive control.. ... Hasegawa, RP; Peterson, BW; Goldberg, ME (August 2004). "Prefrontal neurons coding suppression of specific saccades". Neuron. ... doi:10.1016/j.neuron.2004.07.013. PMID 15294148.. *^ Hillyard, SA; Anllo-Vento, L (February 1998). "Event-related brain ...
The anatomical core of the reward system are dopaminergic neurons of the ventral tegmentum that project to the nucleus ... Dense connections exist between monoaminergic neurons. Dopaminergic neurotransmission regulates the activity of 5-HT and NE in ... Patients taking strong dopaminergic antagonists such as those used in the treatment of psychosis are more likely than the ... However, it was still shown to facilitate dopaminergic neurotransmission in certain brain regions such as in the core of the ...
This increased chloride ion influx hyperpolarizes the neuron's membrane potential. As a result, the difference between resting ... A single dose of diazepam modulates the dopamine system in similar ways to how morphine and alcohol modulate the dopaminergic ... limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture". Journal of Pharmacology ...
Parkinson's disease is a chronic neurodegenerative disorder that involves the loss of dopaminergic neurons in the brain. While ...
Nicotine Activity on Dopaminergic Neurons edit *^ The interactive pathway map can be edited at WikiPathways: " ...
Talk:Dopaminergic cell group A8. *Talk:Dopaminergic cell group A9. *Talk:Dopaminergic cell group A10 ... Talk:Anaxonic neuron. *Talk:Angular bundle. *Talk:Ansa lenticularis. *Talk:Anterior ethmoidal nerve ...
A consistent abnormality in Parkinson's disease is degeneration of dopaminergic neurons in the substantia nigra, leading to a ... neuron projection. • cytoplasmic side of plasma membrane. • cell nucleus. • synaptic vesicle. • melanosome membrane. • terminal ... synaptic transmission, dopaminergic. • circadian sleep/wake cycle. • cellular response to drug. • multicellular organism aging ... peripheral sympathetic neurons and the adrenal medulla.[6] Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan ...
... evidence for independent modulation of prefrontal functions by midbrain dopaminergic and noradrenergic neurons. Front. Neural ... dopaminergic pathway)和腦內去甲腎上腺素通道系統/藍斑核系統。它們主要的工作就是負責調節執行功能(認知
Bentué-Ferrer D, Reymann JM, Tribut O, Allain H, Vasar E, Bourin M (February 2001). "Role of dopaminergic and serotonergic ... of GABAergic neurons. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to ...
Carta M, Allan AM, Partridge LD, Valenzuela CF (2003). "Cocaine inhibits 5-HT3 receptor function in neurons from transgenic ... "Regulation of dopaminergic transmission and cocaine reward by the Clock gene". Proc Natl Acad Sci USA 102 (26): 9377-81. doi ...
Current research links cystatin B to production of inhibitory neurons known as GABAergic neurons. It has shown that a lack of ... Substantial Thalamostriatal Dopaminergic Defect in Unverricht-Lundborg Disease. Epilepsia 48(9):1763-73 ... Studies suggest that the absence of cystatin B leads to the death of affected neurons, leading to a damaged portion of the ... Normally, after a seizure, the presence of cystatin B prevents the neurons from dying due to toxic levels of neurotransmitters ...
... simultaneously releasing excitatory neurotransmitters onto motor neurons. Because the number and function of GABAB receptors ... and other anticonvulsant drugs GHB receptor antagonist NCS-382 GABAA receptor modulators uridine acamprosate dopaminergic ... is a critical finding since myelin is the electrical and insulating phospholipid layer that surrounds the axons of many neurons ...
As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is ... "Neuron. 86 (3): 646-664. doi:10.1016/j.neuron.2015.02.018. PMC 4425246. PMID 25950633. An important goal in future for ... Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of ... Dopaminergic psychostimulantsEdit. Amphetamine improves task saliency (motivation to perform a task) and increases arousal ( ...
Cortical inputs to thalamic neurons enable attentional modulation of sensory neurons. Dysfunction in sensory afferents, and ... Dopaminergic and serotoninergic hallucinationsEdit. It has been reported that in serotoninergic hallucinations, the person ... and the cholinergic neurons in the parabrachial area and pedunculopontine nuclei of the tegmentum.[25] ... composed of projections between thalamic and cortical neurons and adjacent interneurons, underlie certain electrophysical ...
First Parkinsons patients dosed with dopaminergic neurons. Nature Biotechnology volume 39, page 785 (2021)Cite this article ... The aim is for the DA01 cells to replace the lost dopaminergic neurons, stopping and reversing the degenerative process. The ... BlueRock Therapeutics, a company wholly owned by Bayer AG, initiated the phase 1 study to test DA01 cells, dopaminergic neurons ... First Parkinsons patients dosed with dopaminergic neurons. Nat Biotechnol 39, 785 (2021). https://doi.org/10.1038/s41587-021- ...
They found that loss of Scarlet activity causes a progressive loss of dopaminergic neurons and that Scarlet has a ... fly protein known as Scarlet as a target gene whose function is required to prevent age-dependent loss of dopaminergic neurons ... Fly protein has protective effect on dopaminergic neurons. Lehigh University. Journal. Journal of Cell Science. Keywords. * ... "But why are dopaminergic neurons the ones that are lost? We dont have an answer for why that is." In trying to answer this ...
Specification of dopaminergic and serotonergic neurons in the vertebrate CNS.. Hynes M1, Rosenthal A. ... The early specification of dopaminergic and serotonergic neurons during vertebrate CNS development relies on signals produced ... and candidate signaling systems that control the later development of the dopaminergic system. ...
Retinal dopaminergic amacrine neurons (DA neurons) play a central role in reconfiguring retinal function according to ... Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons.. Zhang DQ1, Wong KY, Sollars PJ, ... Transient and sustained light responses in dopaminergic amacrine neurons. (A and B) Extracellular loose patch recordings from a ... Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons. Proc Natl Acad Sci U S A. 2008 Sep 16; ...
Also disclosed are methods for treating a neurodegenerative disease in a patient by generating dopaminergic neurons in vitro, ... and transplanting them into the brain of the patient, such that the dopaminergic neurons are sufficient to reduce or eliminate ... causing differentiation of the pluripotent cells into dopaminergic neurons. ... Disclosed herein are methods for generating dopaminergic neurons in vitro by inhibiting a pathway component of a TGF-β ...
... consisting of various regions with particular functions and approximately 100 billion neurons. This complexity has presented a ... One gene, Ptf1a, was only expressed in dopaminergic neurons/coronet cells, but not in any other neurons, so we then analyzed it ... Sea squirt model reveals key molecules in dopaminergic neuron differentiation. *Download PDF Copy ... are vital for the emergence of dopaminergic neurons/coronet cells, a simple early form of the hypothalamus. ...
Surprising finding that one type of mature neuron can be converted directly into another could one day lead to new treatments ... Reporting in Stem Cell Reports ("Phenotypic reprogramming of striatal neurons into dopaminergic neuron-like cells in the adult ... to convert directly into dopaminergic (DA) neuron-like cells (iDALs). These neurons displayed markers and electrophysiological ... Dopaminergic Neurons Generated by Unexpected Conversion of Mature Nerve Cells. October 12, 2018. 0 ...
A small proportion of the converted neurons expressed tyrosine hydroxylase (Th), a marker of dopaminergic neurons. ... wondered what triggered the astrocytes to become dopaminergic neurons, instead of some other type of neuron. Cleveland ... Dopaminergic Neurons Conjured from Astrocytes Restore Motion. Go to another part. Series - Joint Keystone Symposia: ... Next, the scientists tested the strategy in a mouse model of PD, in which they obliterated dopaminergic neurons on one side of ...
The synaptic origin of dopaminergic neuron burst firing. Stimulation of glutamatergic inputs onto dopaminergic neurons ... synaptic integration in the dopaminergic neuron and should provide a framework for understanding how the dopaminergic neurons ... An Intrinsic Neuronal Oscillator Underlies Dopaminergic Neuron Bursting. Christopher A. Deister, Mark A. Teagarden, Charles J. ... An Intrinsic Neuronal Oscillator Underlies Dopaminergic Neuron Bursting. Christopher A. Deister, Mark A. Teagarden, Charles J. ...
The results support a role for Nox2 in the 6-OHDA-induced degeneration of dopaminergic neurons and glial cell activation in the ... mice appear to be completely protected from dopaminergic cell loss, whereas the apocynin treatment conferred only a limited ... was observed in neurons and microglial cells, but not in astrocytes (Figure 2). In the SN, was found in neurons and in ... NADPH Oxidase and the Degeneration of Dopaminergic Neurons in Parkinsonian Mice. Marina S. Hernandes. ,1 Cecília C. Café-Mendes ...
KOR activation inhibits dopaminergic neurons. A, A principal neuron filled with biocytin (red) during electrophysiological ... Although direct KOR agonist inhibition did not occur in every VTA dopaminergic neuron, it was observed only in such neurons. ... or pharmacological properties that specifically delineate dopaminergic neurons from non-dopaminergic neurons in the VTA. ... KOR agonist-responsive neurons are a subset of dopaminergic neurons in the VTA, and most, if not all, KOR agonist-responsive ...
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... receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinsons disease (PD ... Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals ... Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. Downregulation of either parkin ... converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons ...
Visualization, direct isolation, and transplantation of midbrain dopaminergic neurons. Proc Natl Acad Sci U S A. 2001;98(11): ... Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. Durga Praveen Meka,1 Anne Kathrin Müller ... Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem. 2003;278(44):43628- ... Pro-survival role for Parkinsons associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS Biol. 2010;8 ...
... Anne-Marie Arel- ... "Cucurbitacin E Has Neuroprotective Properties and Autophagic Modulating Activities on Dopaminergic Neurons," Oxidative Medicine ...
... neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, ... Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1. By Damian Refojo, Martin Schweizer, ... Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1. By Damian Refojo, Martin Schweizer, ... Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1 Message Subject. (Your Name) has ...
Midbrain dopaminergic neurons, whose loss in adults results in Parkinsons disease, can be specified during embryonic ... Induction of midbrain dopaminergic neurons by Sonic hedgehog Neuron. 1995 Jul;15(1):35-44. doi: 10.1016/0896-6273(95)90062-4. ... Midbrain dopaminergic neurons, whose loss in adults results in Parkinsons disease, can be specified during embryonic ... can block dopaminergic neuron induction by floor plate cells. Our results and those of other studies indicate that SHH-N can ...
2 C and D), which is found primarily in A10 DA neurons. Calbindin also was expressed by host striatal neurons (Fig. 2 C and D) ... Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Lars M. ... The presence of numerous AADC-positive neurons negative for TH or DAT can be explained by the presence of 5HT neurons (Fig. 2F ... Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model ...
PD is characterized by the degeneration of dopaminergic (DA) neurons. There exist four pairs of DA neurons in C. elegans ... 1975) Dopaminergic neurons in the nematode Caenorhabditis elegans. J Comp Neurol 163:215-226. ... 2005) Torsin-mediated protection from cellular stress in the dopaminergic neurons of Caenorhabditis elegans. J Neurosci 25:3801 ... 2018) The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against alpha- ...
BDNF and NT-3 all support survival of subpopulations of neural crest-derived sensory neurons; most … ... BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra Nature. 1991 Mar 21;350(6315):230-2. doi: ... Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra. ... BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal ...
Dopaminergic neurons are brain cells whose primary neurotransmitter is dopamine. Degeneration of these cells leads to the ... Glial cell-derived neurotrophic factor promotes the survival and differentiation of dopaminergic neurons and therefore may be ... Caption: Dopaminergic neuron, computer illustration. Dopaminergic neurons are brain cells whose primary neurotransmitter is ... Keywords: 3 dimensional, 3d, artwork, biological, biology, digitally generated, dopamine, dopaminergic neuron, healthcare, ...
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning. By Hsing-Chen Tsai, Feng Zhang, Antoine ... Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning. By Hsing-Chen Tsai, Feng Zhang, Antoine ... Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning Message Subject. (Your Name) has forwarded a ... Natural rewards and drugs of abuse can alter dopamine signaling, and ventral tegmental area (VTA) dopaminergic neurons are ...
... rescuing dopaminergic neurons from apoptosis.27 Sesamin has also been shown to protect dopaminergic neurons derived from PC12 ... confers neuroprotection to rat midbrain dopaminergic neurons. It has been shown to effectively protect dopaminergic neurons ... Curcumin protects dopaminergic neuron against LPS induced neurotoxicity in primary rat neuron/glia culture. ... N9 and PC12 cells differentiated into dopaminergic neurons MPP+ (500μM) ↓ IL-6, IL-1β, and TNF-α. Inhibition of iNOS and O2− ...
... from pre-clinical models into induced dopaminergic (iDA) neurons. We have provided results showing that iDA neurons are ... Direct Reprogramming of Functional, Induced Dopaminergic Neurons from Human Adult Somatic Cells. Research Grant, 2014. This ... In addition, iDA neurons will be explored as a superior source for cell replacement therapeutic approaches in PD in order to ... In addition, human iDA neurons will be transplanted in a model of Parkinson s disease to test their capability of reversing the ...
In the rat model of Parkinsons disease, Fgf20 afforded significant protection against the loss of dopaminergic neurons. The ... These findings indicate the importance of FGF20 for the differentiation and survival of dopaminergic neurons and the etiology ... In the rat model of Parkinsons disease, Fgf20 afforded significant protection against the loss of dopaminergic neurons. The ... These findings indicate the importance of FGF20 for the differentiation and survival of dopaminergic neurons and the etiology ...
... neurons from human pluripotent stem cells (hPSCs) in the absence of gene manipulation is the most desired alternative to ... 2011). Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature, 476, 224-227.CrossRef ... Ang, S. L. (2006). Transcriptional control of midbrain dopaminergic neuron development. Development, 133, 3499-3506.CrossRef ... Direct differentiation of dopaminergic (DA) neurons from human pluripotent stem cells (hPSCs) in the absence of gene ...
Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP ... Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP ... Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP ... Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP ...
Parkinsons disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons ... Pten ablation in adult dopaminergic neurons is neuroprotective in Parkinsons disease models. FASEB J. 25, 2898-2910 (2011).. ... Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons. Development 130, 2535-2542 ... YAP supports dopaminergic neurons. Parkinsons disease (PD) is a neurodegenerative disorder marked by progressive loss of ...
Optimizing dopaminergic differentiation of pluripotent stem cells for the manufacture of dopaminergic neurons for ... Optimizing dopaminergic differentiation of pluripotent stem cells for the manufacture of dopaminergic neurons for ... J Biomol Screen (2013) Using human pluripotent stem cell-derived dopaminergic neurons to evaluate candidate Parkinsons disease ... Cytotherapy (2014) Survival and engraftment of dopaminergic neurons manufactured by a Good Manufacturing Practice-compatible ...
Substantia nigra. Computer illustration showing a healthy substantia nigra (top) and degenerated substantia nigra (bottom) from human brains.
  • In trying to answer this question, Babcock and his team focus on why dopamine-producing neurons selectively die in patients with Parkinson's disease. (eurekalert.org)
  • The University of Texas (UT) Southwestern researchers had originally set out to prompt supporting glial cells to develop into dopamine-producing neurons, but their approach instead triggered a type of GABA-producing striatal nerve cells known as medium spiny neurons, to convert directly into dopaminergic (DA) neuron-like cells (iDALs). (genengnews.com)
  • Dopamine-producing neurons are generally located elsewhere in the brain, but do put out connections that control the striatal medium spiny neurons. (genengnews.com)
  • The team suggests that as well as providing new insights into neuronal plasticity and the maintenance of cell identity, the demonstration that one type of mature neuron in the adult brain can be converted directly into another-without resorting to stem cells-could lead to new treatment strategies for neurological disorders. (genengnews.com)
  • The UT Southwestern scientists' latest work, focused on reprogramming glial cells, was founded on their previous studies indicating that ectopic SOX2 can reprogram resident striatal glial cells in the adult mouse brain into neuronal progenitors, which then differentiate into mature neurons when the animals are treated with the small molecule valproic acid. (genengnews.com)
  • In culture, this oligonucleotide induced the differentiation of mouse or human astrocytes into cells that expressed typical neuronal markers, and that differentiated into different kinds of neurons. (alzforum.org)
  • Because neurons develop from ES cells even when implanted outside the central nervous system ( 11 ) and ectoderm develops into neural tissue when cell-to-cell communication is disrupted by dissociation of the cells ( 12 - 14 ), we hypothesized that dilution of ES cells into single-cell suspensions of low ES cell concentrations would result in neuronal development. (pnas.org)
  • BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease. (nih.gov)
  • In addition, iDA neurons will be explored as a superior source for cell replacement therapeutic approaches in PD in order to restore a dopaminergic neuronal network competent to re-establish dopamine function when necessary. (michaeljfox.org)
  • Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. (springer.com)
  • The alteration of spatial learning abilities of rats induced by nano-MnO 2 may be associated with dopaminergic neuronal dysfunction and astrocyte activation. (mdpi.com)
  • The promise of stem cell therapies in diseases such as Parkinson's disease has renewed the interest in gaining a deeper understanding of the signals and mechanisms that regulate the differentiation of stem/progenitor cells into specific neuronal populations, such as dopaminergic (DA) neurons. (biologists.org)
  • Embryonic and postnatal neurogenesis can therefore generate distinct neuronal subclasses, placing important constraints on the functional roles of adult-born neurons in sensory processing. (elifesciences.org)
  • There was no evidence of neuronal degeneration, astrocyte or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH+) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. (rti.org)
  • To our surprise we observed a dramatic up-regulation of Pin1 mRNA and protein levels in dopaminergic MN9D neuronal cells treated with the parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP + ) as well as in the substantia nigra of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. (pubmedcentralcanada.ca)
  • Furthermore, juglone treatment in the MPTP mouse model of PD suppressed Pin1 levels and improved locomotor deficits, dopamine depletion, and nigral dopaminergic neuronal loss. (pubmedcentralcanada.ca)
  • In recent years the occurrence of non-dopaminergic neuronal loss and non-motor symptoms has been recognized in PD pathology ( 5 , 6 ). (pubmedcentralcanada.ca)
  • Methodology/Principal Findings]: Here we show a novel function of phosphodiesterase 7 inhibition on nigrostriatal dopaminergic neuronal death. (csic.es)
  • We found that S14, a heterocyclic small molecule inhibitor of phosphodiesterase 7, conferred significant neuronal protection against different insults both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures. (csic.es)
  • Using a variety of chemicals that interfere with DNA methylation and histone acetylation, we showed that such epigenetic modifications increased neuronal differentiation but did not enable specific regional patterning, such as midbrain dopaminergic (DA) neuron generation. (harvard.edu)
  • In summary, a murine Pink1 deficiency in serotonergic or dopaminergic neurons did not lead to neuronal degeneration or biochemical changes. (uni-muenchen.de)
  • Modelling realistic morphological and biophysical variations clarify this result: in SNc DA neurons, the complexity of the ABD combined with its excitability predominantly define pacemaking frequency and AP shape, such that large variations in AIS geometry negligibly affect neuronal output, and are tolerated. (yale.edu)
  • In the present research, using both in vivo push-pull perfusion and in vitro superfusion techniques coupled to HPLC assay, the effect of prolactin on nigrostriatal and mesolimbic dopaminergic neuronal activity and its possible regulatory mechanism were examined. (illinois.edu)
  • BU prevented neuronal degeneration in LPS-treated neuron-microglia cocultures. (ovid.com)
  • No other neuronal subtype in the VM was affected suggesting that this role for Ngn2 is specific for the mesDA neurons. (dissertations.se)
  • DESCRIPTION (provided by applicant): This project aims to design innovative scaffolds that will integratively address two critical barriers for treating neurodegenerative diseases: (a) Cell Sourcing: support the maturation, specification, and function of reprogrammed human stem cell-derived neurons in vitro and (b) Subtype-specific Neuronal Transplantation: enable efficacious transplantation to treat neurodegenerative diseases in vivo. (neurodegenerationresearch.eu)
  • These results identify Ral-mediated vesicular release as an effector mechanism of neuronal SOCE in pupal dopaminergic neurons with functional consequences on flight behavior. (eneuro.org)
  • To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. (scielo.org.co)
  • Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders. (scielo.org.co)
  • The mechanisms of progressive dopaminergic neuronal loss in Parkinson's disease (PD) remain poorly understood, largely due to the complex etiology and multifactorial nature of disease pathogenesis. (biomedcentral.com)
  • In this study we used a dopaminergic neuronal cell model and recombinant TNF to characterize intracellular signaling pathways activated during TNF-induced dopaminergic neurotoxicity. (biomedcentral.com)
  • TNF signaling in dopaminergic neuronal cells triggered the activation of protein kinase Cδ (PKCδ), an isoform of the novel PKC family, by caspase-3 and caspase-8 dependent proteolytic cleavage. (biomedcentral.com)
  • Notably, inhibition of PKCδ signaling by small interfering (si)RNA or overexpression of a PKCδ cleavage-resistant mutant protected against TNF-induced dopaminergic neuronal cell death. (biomedcentral.com)
  • DGIST's research team led by Dr. Yun-Il Lee in Well-Aging Research Center has identified a new mechanism of inhibition of dopaminergic neuronal apoptosis and suggested the possibility of preventing and treating Parkinson's disease. (news-medical.net)
  • Thus, we reviewed recent findings relating to degeneration of dopaminergic neurons during metabolic diseases. (frontiersin.org)
  • We highlight the fact that using a metabolic approach to manipulate degeneration of dopaminergic neurons can serve as a therapeutic strategy to attenuate pathology of PD. (frontiersin.org)
  • Here, we review recent studies and provide new insight on the link between metabolic diseases and the degeneration of dopaminergic neurons, which consequently leads to PD. (frontiersin.org)
  • Parkinson disease (PD) is a chronic neurodegenerative disease characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra. (pubmedcentralcanada.ca)
  • In this study, we report that dextromethorphan (DM), an ingredient widely used in antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through inhibition of microglial activation. (aspetjournals.org)
  • Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM (1-10 μM) reduced, in a dose-dependent manner, the microglia-mediated degeneration of dopaminergic neurons induced by lipopolysaccharide (LPS, 10 ng/ml). (aspetjournals.org)
  • The main pathological symptoms include a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNC) and the occurrence of Lewy bodies. (uni-muenchen.de)
  • BU was orally administered to these rats for 7 days, which ameliorated the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and alleviated motor deficits. (ovid.com)
  • Parkinson's disease (PD) involves the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) that is thought to cause the classical motor symptoms of this disease. (inserm.fr)
  • Hypotheses: Work package (WP) A: (i) MtDNA mutations/depletion cause RC dysfunction which in turn triggers degeneration of dopaminergic neurons in IPD. (fnr.lu)
  • The mitochondrial inhibitor 1-methyl-4-phenylpyridinium (MPP(+)) is the toxicologically relevant metabolite of 1-methyl-4-phenyltetrahydropyridine (MPTP), which causes relatively selective degeneration of dopaminergic neurons in the substantia nigra. (uni-konstanz.de)
  • Disclosed herein are methods for generating dopaminergic neurons in vitro by inhibiting a pathway component of a TGF-β signaling pathway and overexpressing one or more cell fate-inducing polypeptides in pluripotent cells, causing differentiation of the pluripotent cells into dopaminergic neurons. (google.com)
  • Also disclosed are methods for treating a neurodegenerative disease in a patient by generating dopaminergic neurons in vitro, and transplanting them into the brain of the patient, such that the dopaminergic neurons are sufficient to reduce or eliminate the symptoms of the neurodegenerative disease. (google.com)
  • iv) culturing said cells in vitro to produce dopaminergic neurons. (google.com)
  • However, an in vitro study using apocynin, a nonspecific pharmacological inhibitor of NADPH oxidase (Nox), suggested that Nox-derived reactive oxygen species (ROS) might be also involved in the 6-OHDA-induced dopaminergic degeneration [ 12 ]. (hindawi.com)
  • Here we show that the amino-terminal product of Sonic hedgehog autoproteolysis (SHH-N), an inductive signal expressed by floor plate cells, can induce dopaminergic neurons in vitro. (nih.gov)
  • Previous work showed that DA neurons can be produced in vitro from ventral mesencephalic (VM) precursor cells ( 7 ). (pnas.org)
  • A problem using expanded fetal VM precursors ( 7 ) is the low in vivo survival rate of 3-5% of the grafted DA neurons, which eliminates the actual gain by in vitro cell number expansion compared with fresh (unexpanded) fetal day-12 VM ( 7 , 8 ). (pnas.org)
  • BDNF, but not NGF, supports the survival of cultured retinal ganglion cells but both NGF and BDNF promote the survival of septal cholinergic neurons in vitro. (nih.gov)
  • VEGF was found to be neuroprotective against cell death of primary E14 murine ventral mesencephalic neurons induced by 6-hydroxydopamine (6-OHDA) treatment in vitro . (wiley.com)
  • We reported previously that exogenous dynorphin exerts potent neuroprotective effects against inflammation-induced dopaminergic neurodegeneration in vitro. (sigmaaldrich.com)
  • The in vivo results presented here extend our previous in vitro findings and further indicate that endogenous dynorphin plays a critical role in protecting dopaminergic neurons through its anti-inflammatory effects. (sigmaaldrich.com)
  • These distinct cellular properties may thus be used to confidently discriminate GABAergic and DAergic neurons in VTA during in vitro electrophysiological recordings. (biomedsearch.com)
  • A mathematical model of midbrain dopamine neurons has been developed in order to understand the mechanisms underlying two types of calcium-dependent firing patterns that these cells exhibit in vitro. (rice.edu)
  • Our in vitro data suggest that this miRNA-embedded silencing vector may be ideal for chronic in vivo SNCA gene silencing in DA neurons. (luriechildrens.org)
  • CDI's manufacturing capabilities enable these specialized neurons to be developed at a high purity and quantity with rigorous quality control so that researchers studying dopaminergic diseases have a stable supply source of a relevant in vitro model. (technologynetworks.com)
  • The neurotrophic effects of the BB isoform of platelet-derived growth factor (PDGF) on rat and human fetal mesencephalic dopaminergic neurons have been characterized in vitro. (lu.se)
  • This concentration resulted in a marked increase in the survival and neurite outgrowth from rat and human tyrosine hydroxylase-(TH) positive, presumed dopaminergic neurons after 7 days in vitro. (lu.se)
  • We will extensively characterize the in vitro and in vivo functions of AFLN-induced mDA neurons. (kennedykrieger.org)
  • However, the mechanisms of specification of mesDA neurons in vivo need to be elucidated for identification and generation of mesencephalic dopaminergic (mesDA) neurons from stem cells in vitro. (dissertations.se)
  • The central hypothesis is that 3D engineered microscale niches (EMNs) based on nanofibrous hydrogel scaffolds can support the induction and maturation of subtype specific neurons in vitro prior to transplantation and promote the survival and enhanced functional interaction with host tissue following transplantation. (neurodegenerationresearch.eu)
  • Compelling evidence over the last decade from animal models, in vitro studies and PD patients has demonstrated that the protracted neuroinflammation that occurs in the SNpc can exacerbate the degeneration of vulnerable dopaminergic neurons. (biomedcentral.com)
  • Dopaminergic cells are derived from SOX- floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. (nus.edu.sg)
  • They found that loss of Scarlet activity causes a progressive loss of dopaminergic neurons, induces locomotor defects, shortens lifespan and functions cell autonomously within dopaminergic neurons. (eurekalert.org)
  • Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the nigrostriatal pathway of the brain, which triggers complex functional modifications within the basal ganglia circuitry. (hindawi.com)
  • Parkinson's disease (PD) is a neurodegenerative disorder marked by progressive loss of dopaminergic neurons and motor control. (sciencemag.org)
  • Pathologically, the disease is characterized by gliosis, progressive loss of dopaminergic neurons and their terminals in the nigrostriatal axis, and appearance of cytoplasmic inclusions known as Lewy bodies in the surviving neurons of substantia nigra (SN) ( 2 - 4 ). (pubmedcentralcanada.ca)
  • Fibiger, H. C. 1978-03-01 00:00:00 Abstract- In order to examine the hypothesis that acetylcholinesterase (AChE) is contained within dopaminergic neurons of the nigro‐striatal projection, the effects of selective destruction of these neurons by 6‐hydroxydopamine (6‐OHDA) on cholinesterase, tyrosine hydroxylase, and choline acetyltransferase in substantia nigra (SN) and caudate‐putamen (CP) were studied in the rat. (deepdyve.com)
  • In this study, we investigated the autophagy and apoptosis induced by ATR in dopaminergic neurons in vivo . (mdpi.com)
  • The current work led to the following conclusions: (1) The spontaneous afternoon-evening increase in in vivo 3,4-dihydroxyphenylacetic acid (DOPAC) output from the terminals but not from the somatodendrites of the mesostriatal dopaminergic system suggest a changes in presynaptic control. (illinois.edu)
  • We hypothesize that a self-functioning E-DA mini neural circuitry within a microscaffold environment will provide sufficient excitatory drive to promote enhanced functional interaction of DA neurons with host tissue in vivo. (neurodegenerationresearch.eu)
  • We use a realistic computational model of dopaminergic neurons in vivo to suggest that ethanol, through its effects on Ih, modifies the temporal structure of the spiking activity. (yale.edu)
  • We confirmed the results from our mechanistic studies in primary embryonic mesencephalic cultures and in vivo using the stereotaxic lipopolysaccharide (LPS) model of nigral dopaminergic degeneration. (biomedcentral.com)
  • We report here the post-transcriptional regulation of DRD2 expression by two brain-expressed microRNAs (miRs), miR-326 and miR-9, in an ex vivo mode, and show the relevance of miR-mediated DRD2 expression regulation in human dopaminergic neurons and in developing human brains. (readbyqxmd.com)
  • 7. The method of claims 1 , wherein said dopaminergic neurons express a phenotype of A9 dopaminergic neurons. (google.com)
  • Reporting in Stem Cell Reports (" Phenotypic reprogramming of striatal neurons into dopaminergic neuron-like cells in the adult mouse brain ,") they conclude, "Such knowledge may one day be applied to devise therapeutic strategies for treating neurological diseases through reprogramming the phenotype of local neurons. (genengnews.com)
  • The midbrain ventral tegmental area (VTA) contains neurons largely with either a dopaminergic (DAergic) or GABAergic phenotype. (biomedsearch.com)
  • This suggests that Nurr1 and Ngn2 interact to specify a more mature dopaminergic phenotype. (dissertations.se)
  • Thus, GDNF may mediate plasticity in the dopamine-depleted primate brain, which may serve to compensate for cell loss by converting striatal neurons to a dopaminergic phenotype. (epfl.ch)
  • Here, we show that knockdown of components of a Ral effector, the exocyst complex, in pupal neurons also leads to reduced flight bout durations, and this phenotype derives primarily from dopaminergic neurons. (eneuro.org)
  • LIM homeodomain transcription factor Lmx1a is essential for chick mdDA development, and for the efficient differentiation of ES-cells towards a dopaminergic phenotype. (semanticscholar.org)
  • Parkinson's disease is a neurodegenerative disorder that affects dopamine-producing or dopaminergic neurons. (eurekalert.org)
  • Identifying the genes that underlie the loss of these neurons is important to understanding how the disease functions, according to Patrick Cunningham, a PhD student at Lehigh University in Bethlehem, Pennsylvania, where he is investigating the loss of dopaminergic neurons in Drosophila in a model for Parkinson's disease. (eurekalert.org)
  • So people who have a mutation that might render them vulnerable to Parkinson's disease tend to lose dopaminergic neurons," Babcock says. (eurekalert.org)
  • In an interview for the journal's "First Person" section, first author Cunningham says: "When I was looking at the rescue experiment to see if Scarlet was neuroprotective in a Parkinson's disease model I counted the dopaminergic neurons, and, in brain after brain, I saw that they survived. (eurekalert.org)
  • This characterization of the way in which different subpopulations of neurons are created, albeit in a simple precursor to the human hypothalamus, could help in the fight against human diseases involving dopaminergic deficiencies such as Parkinson's disease. (news-medical.net)
  • In a serendipitous bit of cell reprogramming sleight of hand, scientists have unwittingly managed to convert mature inhibitory neurons in the brains of live adult mice directly into neurons that resemble the dopamine-producing nerve cells that are lost in Parkinson's disease. (genengnews.com)
  • Parkin and the glial cell line-derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson's disease (PD). (jci.org)
  • Midbrain dopaminergic neurons, whose loss in adults results in Parkinson's disease, can be specified during embryonic development by a contact-dependent signal from floor plate cells. (nih.gov)
  • Will embryonic stem cells be a useful source of dopamine neurons for transplant into patients with Parkinson's disease? (pnas.org)
  • Such DA neurons can restore cerebral function and behavior in an animal model of Parkinson's disease. (pnas.org)
  • Parkinson's disease (PD) is a degenerative disorder characterized by a loss of midbrain dopamine (DA) neurons with a subsequent reduction in striatal DA ( 1 ). (pnas.org)
  • Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. (elsevier.es)
  • In the rat model of Parkinson's disease, Fgf20 afforded significant protection against the loss of dopaminergic neurons. (frontiersin.org)
  • Fgf20 promoted the differentiation of these stem cells into dopaminergic neurons, which attenuated neurological symptoms in animal models of Parkinson's disease. (frontiersin.org)
  • These findings indicate the importance of FGF20 for the differentiation and survival of dopaminergic neurons and the etiology and therapy of Parkinson's disease. (frontiersin.org)
  • As these findings indicate that FGF20 may provide useful clues on the etiology and therapy of Parkinson's disease, a succinct review on the roles of FGF20 in dopaminergic neurons and Parkinson's disease has been provided. (frontiersin.org)
  • 2011). Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. (springer.com)
  • Parkinson's disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. (sciencemag.org)
  • Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of midbrain dopaminergic (mDA) neurons in the substantia nigra, which results in the main motor symptoms of disease ( 1 ). (sciencemag.org)
  • Develop a scalable GMP compatible process for production of clinical grade dopaminergic neurons from hESCs and/(or) hiPSCs to support the development of a therapeutic cell candidate for Parkinson's disease (PD), and generate sufficient supporting data from scalable culture to make a case to move to pre-clinical development work. (ca.gov)
  • Parkinson's disease (PD) is a devastating movement disorder caused by the death of dopaminergic neurons (a type of nerve cells in the central nervous system) present in the midbrain. (ca.gov)
  • To unveil the participation of the Rho GTPase family to the molecular pathogenesis of Parkinson's disease, we first used C elegans to demonstrate the role of the small GTPase RAC1 ( ced-10 in the worm) in maintaining dopaminergic function and survival in the presence of alpha-synuclein. (springer.com)
  • Further, by using dopaminergic neurons derived from patients of familial LRRK2-Parkinson's disease we report that human RAC1 activity is essential in the regulation of dopaminergic cell death, alpha-synuclein accumulation, participates in neurite arborization and modulates autophagy. (springer.com)
  • Thus, we determined for the first time that RAC1/ced-10 participates in Parkinson's disease associated pathogenesis and established RAC1/ced-10 as a new candidate for further investigation of Parkinson's disease associated mechanisms, mainly focused on dopaminergic function and survival against α-synuclein-induced toxicity. (springer.com)
  • During the Summer School on Dopaminergic Neurons , organised by SISSA and CBM, the most innovative approaches to treat Parkinson's disease will be handled. (sissa.it)
  • Among them, Parkinson's disease and the most innovative approaches to treat it, as well as the most recent discoveries on the processes triggering this disorder, will be handled at the Summer School on Dopaminergic Neurons , organised by the International School for Advanced Studies (SISSA) and by the Centre of Molecular Biomedicine (CBM), and held at SISSA on Thursday and Friday. (sissa.it)
  • Such activations could contribute to reestablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease. (osti.gov)
  • This study examined whether the cannabinoid receptor type 1 (CB 1 ) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. (jimmunol.org)
  • Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. (jimmunol.org)
  • In the present study, we demonstrated that bee venom phospholipase A 2 (bvPLA 2 ) is the major BV compound capable of inducing Treg expansion and promotes the survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. (jimmunol.org)
  • DA neurons derived from Oct4-reprogrammed NSCs improved behavioural motor deficits in a rat model of Parkinson's disease (PD) upon intrastriatal transplantation. (harvard.edu)
  • These studies suggest that Nurr1 protects against loss of dopaminergic neurons in Parkinson's disease in part by limiting the production of neurotoxic mediators by microglia and astrocytes. (ca.gov)
  • Cell replacement therapy could be an important treatment strategy for Parkinson's disease (PD), which is caused by the degeneration of dopamine neurons in the midbrain (mDA). (jefferson.edu)
  • Lorenz Studer, M.D., director, Center for Stem Cell Biology at Memorial Sloan Kettering Cancer Center, said, "We are pleased that Cellular Dynamics has licensed our technology to create dopaminergic neurons for research use that are specific to the substantia nigra, the small area of the brain implicated in Parkinson's disease. (technologynetworks.com)
  • Research in our laboratory has shown that iPSC-derived dopaminergic neurons that follow the midbrain dopaminergic developmental pathway are able to engraft in animal models for Parkinson's disease. (technologynetworks.com)
  • The extensive degeneration of mesostriatal dopamine (DA) neurons in patients with Parkinson's disease lead to severe motor deficits with tremor, rigidity and hypokinesia. (springer.com)
  • Ventral midbrain dopaminergic (mDA) neurons derived from human induced pluripotent stem cells (iPSCs) provide a unique cell resource for disease modeling, drug development and cell replacement therapy for Parkinson's disease (PD). (kennedykrieger.org)
  • We have generated organoids rich in midbrain dopaminergic (DA) neurons, the specific cells which degenerate in Parkinson's Disease (PD). (labroots.com)
  • We will evaluate the ability of self-actuating EMNs of E and DA neurons to improve functional deficits in the Parkinson's disease symptoms, and again examine maturation outcomes of transplanted cells and innervated host tissues. (neurodegenerationresearch.eu)
  • Moran, Steven 1995-01-30 00:00:00 A unilateral partially lesioned rat model of Parkinson's disease was developed following selective lesioning of the dopamine neurons of the substantia nigra pars compacta by stereotactic injection of the neurotoxin 6-hydroxydopamine. (deepdyve.com)
  • These results support the utility of unilateral partially lesioned rat models of Parkinson's disease for studies investigating a host sprouting or upregulation response and confirm that the immunostained striatal fibers originate from spared dopamine neurons in the ventromedial midbrain. (deepdyve.com)
  • This executive function has been linked to the cholinergic and dopaminergic systems through pharmacological interventions, but effective mediation of working memory disorders, such as Alzheimer's and Parkinson's disease, has been unsuccessful. (princeton.edu)
  • Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson's disease. (inserm.fr)
  • Background: Parkinson's disease (PD) is characterized by a selective loss of dopaminergic neurons, Lewy body formation and respiratory chain (RC) complex I (CI) deficiency in the substantia nigra (SN). (fnr.lu)
  • In their experimental therapy, the team of researchers "reprogrammed" stem cells to make them neurons and implanted them into the brain of monkeys with a version of Parkinson's disease. (news-medical.net)
  • A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. (ca.gov)
  • Home › About CIRM › Our Publications › Grantee publications › A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. (ca.gov)
  • We have provided results showing that iDA neurons are functional and competent to produce and release dopamine and to establish synapses. (michaeljfox.org)
  • We plan to establish a superior protocol of genetic reprogramming suitable for converting human adult fibroblasts into functional iDA neurons with high efficiency. (michaeljfox.org)
  • In addition, human iDA neurons will be transplanted in a model of Parkinson s disease to test their capability of reversing the diseased state and re-establishing a functional dopaminergic system. (michaeljfox.org)
  • 2008). Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. (springer.com)
  • Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. (springer.com)
  • The functional role of this opioid peptide in the regulation of mesencephalic dopaminergic (DAergic) neurons is not clear. (sigmaaldrich.com)
  • The functional properties of mature postnatally-generated neurons often match those of their embryonically-produced counterparts. (elifesciences.org)
  • Here we report for the first time the successful differentiation of SVZ adult NSCs into functional region-specific midbrain DA neurons, by means of Oct-4 induced pluripotency. (harvard.edu)
  • Anden N-E, Dahlstrom A., Fuxe K., Larsson K.: Functional role of the nigro-striatal dopamine neurons. (springer.com)
  • The goal of this aim is to establish a convenient and reliable approach for rapidly generating highly pure, functional and transplantable mDA neurons from both normal and PD-patient-derived iPSCs. (kennedykrieger.org)
  • In this work we have produced midbrain organoids with functional DA neurons while reducing our time and effort. (labroots.com)
  • When patterned with SHH and FGF8, the cells were effectively converted to functional Nurr1+ and TH+ dopaminergic cells which accounts for more than 98% of the whole population. (nus.edu.sg)
  • The genes were delivered by viral vector directly into the striatum, a region of the brain that is rich in GABA-producing medium spiny neurons, a nerve cell type that controls motor function. (genengnews.com)
  • Silencing the RNA-binding protein PTB converted astrocytes into neurons within the mouse striatum. (alzforum.org)
  • Taken together, these observations indicate that parkin and the RET signaling cascade converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons and their innervation in the striatum. (jci.org)
  • We show that transplanting low doses of undifferentiated mouse embryonic stem (ES) cells into the rat striatum results in a proliferation of ES cells into fully differentiated DA neurons. (pnas.org)
  • A low cell concentration decreases ES cell-to-cell contact and increases the influence from the adult host striatum, which in contrast to adult neurogenic regions may restrict cell migration and proliferation, thus allowing default differentiation ( 15 - 17 ) into neurons in this paradigm. (pnas.org)
  • A protein partially purified from bovine striatum, a target of nigral dopaminergic neurons, with characteristics apparently similar to those of BDNF, can enhance the survival of dopaminergic neurons in mesencephalic cultures. (nih.gov)
  • Further, rats receiving a continuous infusion of VEGF into the striatum via encapsulated hVEGF-secreting cells (baby hamster kidney-VEGF) displayed a significant decrease in amphetamine-induced rotational behavior and a significant preservation of tyrosine hydroxylase-positive neurons and fibers compared with control animals. (wiley.com)
  • Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. (jimmunol.org)
  • Previous studies indicate that 80-95% of grafted dopamine neurons die following implantation of embryonic ventral mesencephalic tissue into the striatum. (lu.se)
  • In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). (unboundmedicine.com)
  • Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. (unboundmedicine.com)
  • Clinical trials have shown that cell replacement therapy, where dopaminergic neuroblasts derived from fetal ventral mesencephalon (VM) are transplanted to the striatum, may be an alternative to pharmacological treatment of PD patients. (dissertations.se)
  • The second aim will be focused on transplanting self-actuating EMNs of DA and excitatory neurons into the striatum of a mouse PD model. (neurodegenerationresearch.eu)
  • We will transplant the self-actuating EMNs of E and DA neurons into the striatum of mice lacking DA innervations. (neurodegenerationresearch.eu)
  • Following discrete tracer injections into the striatum adjacent to a cograft, neurons in the medial substantia nigra and ventral tegmental area (areas A9 and A10, respectively) were labelled with Lucifer yellow. (deepdyve.com)
  • The primate striatum contains tyrosine hydroxylase (TH)-immunoreactive (ir) neurons, the numbers of which are augmented after dopamine depletion. (epfl.ch)
  • The effect of GDNF on TH-ir neurons intrinsic to the striatum has yet to be investigated. (epfl.ch)
  • Using neurochemical and genetic tools, we determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid-containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. (sciencemag.org)
  • Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. (sciencemag.org)
  • Distinct cellular properties of identified dopaminergic and GABAergic neurons in the mouse ventral tegmental area. (biomedsearch.com)
  • Physiological and pharmacological properties of DAergic neurons have been determined using tyrosine hydroxylase (TH) immunohistochemistry but many properties overlap with non-DAergic neurons presumed to be GABAergic. (biomedsearch.com)
  • This study examined properties of GABAergic neurons, non-GABAergic neurons and TH-immunopositive neurons in VTA of GAD67-GFP knock-in mice. (biomedsearch.com)
  • Medium spiny neurons (MSNs), which are only GABAergic projection neurons in NAc, also innervate adjacent MSNs, forming the lateral inhibition network. (readbyqxmd.com)
  • Protein transduction-based methods could be efficient, safe approaches to enhance direct differentiation of human embryonic stem cells (hESCs) to DA neurons. (springer.com)
  • Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells. (semanticscholar.org)
  • Derivation of dopaminergic cells from human embryonic stem cells (hESCs) could provide new options for PD therapy. (nus.edu.sg)
  • Moreover, these experiments represent the first characterization of AChE from a homogeneous population of non‐cholinergic neurons in mammalian CNS. (deepdyve.com)
  • A significant decrease in performance accuracy occurred when dopaminergic neurons in the SNc were inhibited, but no change in accuracy was detected when cholinergic neurons in the NB were selectively inhibited. (princeton.edu)
  • Based on these results, it is evident that dopaminergic neurons in the SNc play a significant role in working memory, whereas the role of NB cholinergic neurons may have a secondary or non-causal role in working memory, warranting further investigation. (princeton.edu)
  • mice appear to be completely protected from dopaminergic cell loss, whereas the apocynin treatment conferred only a limited neuroprotection. (hindawi.com)
  • Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration. (jci.org)
  • Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. (jci.org)
  • We have shown previously that mouse ES cells transplanted to normal mice or 6-hydroxydopamine (OHDA)-lesioned rats can differentiate spontaneously into tyrosine hydroxylase (TH)-positive and serotonin (5HT)-positive neurons. (pnas.org)
  • YAP was activated in midbrain dopaminergic neurons in culture and in mice through an interaction between an integrin and the extracellular matrix protein laminin-511. (sciencemag.org)
  • Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. (sciencemag.org)
  • Endogenous dynorphin protects against neurotoxin-elicited nigrostriatal dopaminergic neuron damage and motor deficits in mice. (sigmaaldrich.com)
  • PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. (unboundmedicine.com)
  • In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. (unboundmedicine.com)
  • Male and female C57BL/6J mice were administered diquat dibromide (DQBr2) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. (rti.org)
  • In order to understand the underlying mechanism of the Pink1 deficiency-related phenotypes and to uncover possible compensatory mechanisms, transgenic mice with a specific KO of Pink1 in serotonergic or dopaminergic neurons were analysed at young and middle age (mid-aged). (uni-muenchen.de)
  • TIDA neurone numbers are deficient in Ames (df/df) and Snell (dw/dw) dwarf mice, which lack prolactin, growth hormone and thyroid-stimulating hormone. (ovid.com)
  • Prolactin therapy initiated before 21 days maintains normal-sized TIDA neurone numbers in df/df mice and, when initiated as early as 7 days, maintains the maximum TIDA neurone numbers observed in dw/dw development, which are decreased compared to those in normal mice. (ovid.com)
  • Among saline, 5 μg oPRL and 50 μg oPRL treatments, but not rmPRL, A14 neurone numbers were higher (P ≤ 0.01) in normal compared to in dw/dw mice. (ovid.com)
  • The data obtained in the present study indicate that oPRL, but not rmPRL, when given at a high enough dose, induces TIDA neurone differentiation in dw/dw mice. (ovid.com)
  • Indeed, DJ-1 −/− mice show progressive adult degeneration of SNc mDA neurons upon backcrossing to an appropriate genetic background [7] , indicating that many factors are necessary in order to model polygenic diseases such as PD. (prolekare.cz)
  • In particular, Pitx3-deficient mice exhibit developmental loss of Pitx3-positive Calbindin (Calb)-negative mDA neurons of the vSNc (Pitx3-dependent) while Pitx3-negative Calb-positive mDA neurons of dSNc and VTA (Pitx3-independent) remain essentially unaffected by Pitx3 deficiency [15] . (prolekare.cz)
  • In addition, nicotine failed to significantly activate VTA DAergic neurons in mice that did not express either α4 or α6 nAChR subunits. (aspetjournals.org)
  • Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in the transgenic mice at advanced ages. (ijbs.com)
  • Interestingly, concomitant overexpression of normal TDP-43 and mutant α-synuclein caused a more severe loss of dopaminergic neurons in the double transgenic mice as compared to single-gene transgenic mice. (ijbs.com)
  • Further, primary dopaminergic neurons obtained from PKCδ knockout (−/−) mice were resistant to TNF toxicity. (biomedcentral.com)
  • At the joint symposia Neurodegenerative Diseases: New Insights and Therapeutic Opportunities, and Neural Environment in Disease: Glial Responses and Neuroinflammation, held June 16-21 in Keystone, Colorado, Don Cleveland of the University of California, San Diego, reported on an experimental protocol whereby dialing down expression of a single gene transformed astrocytes into dopaminergic neurons within the substantia nigra of the mouse brain. (alzforum.org)
  • Li, B.-X. Atrazine Causes Autophagy- and Apoptosis-Related Neurodegenerative Effects in Dopaminergic Neurons in the Rat Nigrostriatal Dopaminergic System. (mdpi.com)
  • Finally, S14 neuroprotective effects were reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase A. [Conclusions/Significance]: Our findings demonstrate that phosphodiesterase 7 inhibition can protect dopaminergic neurons against different insults, and they provide support for the therapeutic potential of phosphodiesterase 7 inhibitors in the treatment of neurodegenerative disorders, particularly Parkinson disease. (csic.es)
  • Parkinsons disease (PD) is a neurodegenerative disorder where dopaminergic neurons of the substantia nigra (SNc) in the mesencephalon are progressively eliminated. (dissertations.se)
  • Parkinson¿s disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurones. (nus.edu.sg)
  • Other commercially available iPSC-derived dopaminergic neurons do not follow this developmental path, but instead are derived from neural stem cells. (technologynetworks.com)
  • Preparation and co-culture of iPSC-derived dopaminergic neurons and astrocytes. (janelia.org)
  • Levels of iron and other elements were measured using sensitive and specific wavelength dispersive electron probe x-ray microanalysis coupled with cathodoluminescence spectroscopy in individual substantia nigra dopaminergic neurons. (neurology.org)
  • 1 . Moubarak E, Engel D, Dufour MA, Tapia M, Tell F, Goaillard JM (2019) Robustness to Axon Initial Segment Variation Is Explained by Somatodendritic Excitability in Rat Substantia Nigra Dopaminergic Neurons. (yale.edu)
  • Retinal dopaminergic amacrine neurons (DA neurons) play a central role in reconfiguring retinal function according to prevailing illumination conditions, yet the mechanisms by which light regulates their activity are poorly understood. (nih.gov)
  • Through this procedure, it will be, then, possible to facilitate and accelerate the production of disease-affected iDA neurons for studying in the dish multiple pathogenetic mechanisms of PD with relevant patient s cells. (michaeljfox.org)
  • Current treatment strategies for PD patients are targeted to symptoms, and thus, there is a need to identify mechanisms that could prevent mDA neuron loss. (sciencemag.org)
  • Much of the work aiming at identifying mechanisms supporting mDA neuron differentiation and survival has focused on transcription factors and secreted factors such as morphogens and neurotrophic factors ( 2 ). (sciencemag.org)
  • VEGF likely functions via direct mechanisms by signaling through the neuropilin receptor expressed upon dopaminergic neurons in response to 6-OHDA treatment. (wiley.com)
  • The mechanisms underlying the selective death of substantia nigra (SN) neurons in Parkinson disease (PD) remain elusive. (sigmaaldrich.com)
  • In particular, it is unknown whether mechanisms underlying dopaminergic control of reproduction are shared between mammals and teleost fish. (biologists.org)
  • Researchers from the Higher School of Economics, Ecole Normale Supérieure, Paris, Indiana University and the Russian Academy of Sciences Nizhny Novgorod Institute of Applied Physics have identified potential alcoholism mechanisms, associated with altered dopaminergic neuron response to complex dynamics of prefrontal cortex neurones affecting dopamine release. (news-medical.net)
  • Perhaps only by converting to neurons could astrocytes-forever the wallflowers of brain research-spark this much excitement at a neurodegeneration meeting. (alzforum.org)
  • Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors, including cytokines, reactive oxygen intermediates, nitric oxide, and eicosanoids that impact on neurons to induce neurodegeneration. (aspetjournals.org)
  • Rodent animal models based on genes that participate in development and survival of mDA neurons (Pitx3, Nurr1, Girk2, En1/2, Otx2, etc) have proved extremely useful, especially in defining the candidate cellular pathways underlying the respective differential vulnerability of SNc versus VTA mDA neuron subpopulations to toxin-induced neurodegeneration and in human pathology [9] - [11] . (prolekare.cz)
  • We examined dopaminergic neurotoxicity by using an automated video tracking system, HPLC, immunocytochemistry, and reverse transcription and polymerase chain reaction (RT-PCR). (sigmaaldrich.com)
  • Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. (jimmunol.org)
  • This conclusion was further supported by the finding that DM failed to prevent 1-methyl-4-phenylpyridinium- or β-amyloid peptide (1-42)-induced dopaminergic neurotoxicity in neuron-enriched cultures. (aspetjournals.org)
  • Cucurbitacin E Has Neuroprotective Properties and Autophagic Modulating Activities on Dopaminergic Neurons," Oxidative Medicine and Cellular Longevity , vol. 2014, Article ID 425496, 15 pages, 2014. (hindawi.com)
  • In midbrain dopamine neurons, anatomical evidence for the presence of dendritic spines has been mixed with some studies observing the presence of spine-like processes while others concluding that dopamine neurons are largely aspiny. (nih.gov)
  • Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra. (nih.gov)
  • Activation of the transcription factor YAP by an extracellular laminin promotes the differentiation and survival of dopaminergic neurons. (sciencemag.org)
  • Loss of dopaminergic neurons is seen in Parkinson s disease, and transplantation of these neurons can greatly ease symptoms. (michaeljfox.org)
  • We hypothesize that dopaminergic neurons can be created from other cell types in the adult brain, thereby compensating for the neurons lost in Parkinson s disease. (michaeljfox.org)
  • The generation of new dopaminergic neurons in the adult brain may have direct impact on devising a novel therapeutic strategy for Parkinson s disease. (michaeljfox.org)
  • The biological function of these newly created dopaminergic neurons will be examined in a pharmacologically induced model of Parkinson s disease. (michaeljfox.org)
  • Moreover, after transplantation in a model of Parkinson s disease, iDA neurons survive and integrate in the host tissue and support a significant behavioral rescue of the motor symptoms. (michaeljfox.org)
  • This study will establish efficient protocols for generating iDA neurons through direct conversion of adult fibroblasts from healthy donors as well as people with idiopathic or genetic forms of Parkinson s disease. (michaeljfox.org)
  • Direct differentiation of dopaminergic (DA) neurons from human pluripotent stem cells (hPSCs) in the absence of gene manipulation is the most desired alternative to clinical treatment of Parkinson disease. (springer.com)
  • Durante la Summer School on Dopaminergic Neurons , organizzata da SISSA e CBM, si affronteranno gli approcci più innovativi per curare la malattia di Parkinson. (sissa.it)
  • Fra queste il Parkinson e proprio gli approcci più innovativi per curare questa malattia e le più recenti scoperte sui processi alla base del disturbo sono argomento della Summer School on Dopaminergic Neurons , organizzata dalla Scuola Internazionale Superiore di Studi Avanzati (SISSA) e dal Centro di Biomedicina Molecolare (CBM), che si terrà giovedì e venerdì presso la sede della SISSA. (sissa.it)
  • S14 treatment also reduced microglial activation, protected dopaminergic neurons and improved motor function in the lipopolysaccharide rat model of Parkinson disease. (csic.es)
  • The locomotor deficits associated with Parkinson disease result from the death of a specific subset of dopamine neurons in the ventral part of the midbrain. (prolekare.cz)
  • Parkinson disease (PD) is characterised by the progressive loss of midbrain dopaminergic (mDA) neurons [1] . (prolekare.cz)
  • They developed a cocktail of genes-which they hoped would reprogram glial cells into dopaminergic neurons-including the stem cell factor, SOX2, plus for transcription factors NURR1, LMX1A, and FOXA2, and also administered the compound valproic acid. (genengnews.com)
  • 2010). Foxa2 and Nurr1 synergistically yield A9 nigral dopamine neurons exhibiting improved differentiation, function, and cell survival. (springer.com)
  • Our results demonstrate that Ngn2 is required for the differentiation of Sox2 + ventricular zone progenitors into Nurr1 + postmitotic dopaminergic neuron precursors in the intermediate zone, and that it is also likely to be required for their subsequent differentiation into tyrosine hydroxylase-positive dopaminergic neurons in the marginal zone. (biologists.org)
  • Nurr1, an orphan nuclear receptor, plays an essential role in the generation and maintenance of dopaminergic neurons in the brain. (ca.gov)
  • Reduced Nurr1 expression results in exaggerated inflammatory responses in microglia that are further amplified by astrocytes, leading to the production of factors that cause death of tyrosine hydroxylase-expressing neurons. (ca.gov)
  • FOXA2, LMX1A, NURR1) that drive mDA neuron differentiation. (kennedykrieger.org)
  • Although the neurospheres did not spontaneously give rise to dopaminergic neurons when differentiated, TH-positive cells were detected when Nurr1 was over-expressed in the cultures. (dissertations.se)
  • Furthermore, I found that they expressed other dopaminergic markers which were not seen when either Nurr1 or Ngn2 were over-expressed alone. (dissertations.se)
  • Glial cell-derived neurotrophic factor promotes the survival and differentiation of dopaminergic neurons and therefore may be useful as a treatment. (sciencephoto.com)
  • The effects of PDGF-BB on survival of TH-positive neurons were comparable to those of brain-derived neurotrophic factor (BDNF), whereas neurite outgrowth was more pronounced after addition of BDNF. (lu.se)
  • Glial cell line-derived neurotrophic factor (GDNF) strongly modulates the viability and phenotypic expression of dopamine ventral mesencephalic neurons. (epfl.ch)
  • The neurotrophic factor neurturin can rescue dopaminergic neurons damaged during the disease process. (eurekaselect.com)
  • Significantly, regardless of cell class, KOR-mediated inhibition was found only in tyrosine hydroxylase-immunoreactive and thus dopaminergic neurons. (jneurosci.org)
  • In addition, we found a subset of principal neurons that exhibited both disinhibition by a selective MOR agonist ([ d -Ala 2 , N -Me-Phe 4 , Gly-ol 5 ]-enkephalin) (3 μ m ) and direct inhibition by KOR agonists. (jneurosci.org)
  • several investigators have proposed that the aversive action of systemically administered KOR agonists is mediated primarily by their direct inhibition of DA release from the terminals of VTA neurons in the NAc ( Xi and Stein, 2002 ). (jneurosci.org)
  • Here, we demonstrate, for the first time in teleost fish, dopaminergic control of GnRH1 neurons via direct dopamine receptor type-2 (D2R) mediated inhibition within the hypothalamus. (biologists.org)
  • Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. (pnas.org)
  • Pharmacological treatment with L-DOPA works initially, but reduced efficacy and development of motor complications requires treatment alternatives such as deep brain stimulation and fetal DA neuron transplantation ( 2 ). (pnas.org)
  • There is evidence both from animal models and clinical investigations showing that fetal DA neurons can produce symptomatic relief ( 3 - 6 ). (pnas.org)
  • The limited access and ethical concerns with using fetal tissue have prompted the use of stem cells as a renewable and limitless source of dopaminergic neurons. (dissertations.se)
  • Astrocytes are devoted nurturers of neurons-facilitating synaptic transmission, maintaining the blood-brain barrier, and repairing injuries are but a few of their ministrations. (alzforum.org)
  • At Keystone, Cleveland presented the results of his collaboration with Fu, which took the logical, if ambitious, next step of sparking the conversion of astrocytes into neurons within the brain. (alzforum.org)
  • Fu lab postdoc Hao Qian and colleagues' expression system glowed red in infected astrocytes, and remained red even if the cells converted into neurons. (alzforum.org)
  • This study aimed to observe the effect of intracerebrally injected nano-MnO 2 on neurobehavior and the functions of dopaminergic neurons and astrocytes. (mdpi.com)
  • MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. (jimmunol.org)
  • ModelDB: Nigral dopaminergic neurons: effects of ethanol on Ih (Migliore et al. (yale.edu)
  • Nigral dopaminergic neurons: effects of ethanol on Ih (Migliore et al. (yale.edu)
  • These induced rh-BMSCs exhibited gene/protein expression phenotypes resembling nigral dopaminergic neurons. (eurekaselect.com)
  • The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl- D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). (ufrgs.br)
  • However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. (ufrgs.br)
  • Although several toxin-induced animal models simulate the motor deficits occurring in PD, 6-hydroxydopamine (6-OHDA) lesions have been the most widely used animal models of PD since the 1970s, after the demonstration that the injection of this agent into the substantia nigra pars compacta (SNpc) was able to cause anterograde degeneration of the nigrostriatal dopaminergic system [ 11 ]. (hindawi.com)
  • Ever since, the 6-OHDA model has been accepted as a valuable tool for replicating the PD-like loss of dopaminergic neurons in the SNpc [ 10 ]. (hindawi.com)
  • As paracrine FGFs are local signal molecules, Fgf20 is expected to act on dopaminergic neurons in the SNpc in a paracrine manner. (frontiersin.org)
  • However, as both Fgf20 and Fgfr1 are expressed in most dopaminergic neurons in the SNpc, Fgf20 may act on them in an autocrine/paracrine manner. (frontiersin.org)
  • Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. (unboundmedicine.com)
  • The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. (unboundmedicine.com)
  • In the present study using whole-cell patch-clamp recordings, we demonstrate that a selective KOR agonist (U69593, 1 μ m ) directly inhibits a subset of principal and tertiary but not secondary neurons in the VTA. (jneurosci.org)
  • Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. (sciencemag.org)
  • In mouse midbrain slices, 300 nM nicotine elicited a persistent inward current in VTA DAergic neurons that was blocked by α-conotoxin MII[H9A;L15A], a selective antagonist of nAChRs containing the α6 subunit. (aspetjournals.org)
  • The results suggest that a selective pharmacological remedy could thus be devised against the rewarding effects of ethanol that are postulated to mediate alcohol abuse and addiction, targeting the specific HCN genes expressed in dopaminergic neurons. (yale.edu)
  • In the SN, cholinesterase in dopaminergic neurons was inhibited by the selective AChE inhibitors BW284C51 and ambenonium with a dose‐response curve similar to erythrocyte AChE but different from serum BChE. (deepdyve.com)
  • The selective BChE inhibitor, tetraisopropylpyrophosphoramide, inhibited the enzyme in dopaminergic neurons only at concentrations which inhibited erythrocyte AChE, concentrations somewhat higher than those which inhibited serum BChE. (deepdyve.com)
  • We induced selective lesions of the VTA and SNc DA neurons that did not provoke motor deficits, and showed that bilateral dopamine loss within the SNc, but not within the VTA, induces motivational deficits and affective impairments that mimicked the symptoms of PD patients. (inserm.fr)
  • In mammals, dopamine directly inhibits GnRH1 hypothalamic neurons, the gatekeepers for activation of the HPG axis. (biologists.org)
  • In the hypothalamus, TH-immunoreactive neurons were found in theparaventricular hypothalamic nucleus, periventricular gray, retrochiasmatic area,anterior hypothalamic nucleus of anterior hypothalamic area and retrochiasmatic region of the hypothalamus. (koreamed.org)
  • In the midtuberal region of the hypothalamus, TH-immunoreactive neurons were found in the paraventricular nucleus, dorsomedial hypothalamic nucleus, zona incerta and arcuate nucleus. (koreamed.org)
  • The hypothalamic tuberoinfundibular dopaminergic (TIDA) neurones secrete dopamine, which inhibits prolactin secretion. (ovid.com)
  • Ghrelin activates cells in the anterior pituitary gland and hypothalamic arcuate nucleus, including neuropeptide Y neurons that initiate appetite. (wikipedia.org)
  • These progenitors subsequently divide asymmetrically to generate cells that are fated to differentiate into a neuron, sometimes following additional cycles of cell division. (biologists.org)
  • This suggests that neurosphere expanded cells derived from VM specifically contain progenitors that can generate dopaminergic neurons under certain conditions. (dissertations.se)
  • The results in this thesis have identified a new cellular marker of mesDA progenitors in the developing embryo and also provided new insight into the development of mesDA neurons. (dissertations.se)
  • Lmx1a and lmx1b function cooperatively to regulate proliferation, specification, and differentiation of midbrain dopaminergic progenitors. (semanticscholar.org)
  • The ensuing loss of dopaminergic innervation of the basal ganglia manifests itself as severe motor deficits in PD patients. (dissertations.se)
  • Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta. (ufrgs.br)
  • As the team hoped, the procedure resulted in the development of dopaminergic neuron-like cells in the treated region of the brain, but what they hadn't bargained for was that the new neurons weren't derived from glial cells, but from the direct conversion of medium spiny neurons. (genengnews.com)
  • Self-renewing and multipotent stem cells provide a source of transplantable material to replace post-mitotic neurons that do not spontaneously regenerate after injury. (google.com)
  • Rather than originating from glia, the new dopamine cells came from local, existing mature neurons without passing through a stem cell state," Dr. Zhang states. (genengnews.com)
  • 2012). Identification of embryonic stem cell-derived midbrain dopaminergic neurons for engraftment. (springer.com)
  • Derivation of dopaminergic neurons from pluripotent stem cells. (springer.com)
  • To move forward stem cell-based therapy development it is important to develop scale-up GMP-compatible process of generating therapeutically relevant cells (dopaminergic neurons in this case). (ca.gov)
  • Dopaminergic neurons derived from human induced pluripotent stem cells" by Jingli Cai, Ming Yang et al. (jefferson.edu)
  • Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats. (jefferson.edu)
  • If hiPS cells can be differentiated into authentic mDA neuron, hiPS could provide a potential autologous source of transplant tissue when generated from PD patients, a clear advantage over human embryonic stem (hES) cells. (jefferson.edu)
  • Cellular Dynamics International, Inc. today announced the launch of iCell® DopaNeurons, the company's neural floor plate-derived midbrain dopaminergic neurons generated from human induced pluripotent stem cells (iPSCs). (technologynetworks.com)
  • The first aim is concerned with designing maturation-guiding EMNs of induced pluripotent stem cell (iPSC)-derived reprogrammed dopaminergic (DA) neurons. (neurodegenerationresearch.eu)
  • In most cases, neurons are generated by neural stem cells during brain development and childhood. (wikipedia.org)
  • The team showed that blocking this gene's expression led to a failure of these specific neurons to form, while aberrantly expressing this gene throughout the nervous system converted most of the neurons into this specific type. (news-medical.net)
  • However, without technology to control specific neurons with appropriate temporal precision in freely behaving mammals, the causal role of these action potential patterns in driving behavioral changes has been unclear. (sciencemag.org)
  • Specification of dopaminergic and serotonergic neurons in the vertebrate CNS. (nih.gov)
  • The early specification of dopaminergic and serotonergic neurons during vertebrate CNS development relies on signals produced by a small number of organizing centers. (nih.gov)
  • The neurotransmitter content did not differ in the different brain regions nor did the number of dopaminergic neurons in the SNC or the serotonergic innervation of the OB. (uni-muenchen.de)
  • In conclusion, the serotonergic and dopaminergic system potentially plays a role in the development of PD-related non-motor symptoms upon Pink1 deficiency. (uni-muenchen.de)
  • Since over-expression of human SNCA (hSNCA) leads to death of dopaminergic (DA) neurons in human, rodent and fly brain, hSNCA gene silencing may reduce levels of toxic forms of SNCA and ameliorate degeneration of DA neurons in PD. (luriechildrens.org)
  • The progressive loss of these neurons is what leads to impairment in movement coordination in those suffering from the illness. (eurekalert.org)
  • The team recently identified the fruit fly protein known as Scarlet as a target gene whose function is required to prevent age-dependent loss of dopaminergic neurons in fruit flies, or Drosophila melanogaster. (eurekalert.org)
  • He adds: "This was amazing to observe, because the experiment demonstrated that Scarlet was sufficient in preventing dopaminergic neuron loss, suggesting a neuroprotective function. (eurekalert.org)
  • In addition, LM511-YAP signaling increased the expression of transcription factors critical for mDA identity, such as LMX1A and PITX3, and prevented the loss of mDA neurons in response to oxidative stress, a finding that warrants further investigation to assess therapeutic potential for PD patients. (sciencemag.org)
  • All current treatments attempt to overcome the loss of these neurons by either replacing the lost dopamine, or modulating other parts of the circuit to balance this loss or attempting to halt or delay the loss of dopaminergic neurons. (ca.gov)
  • Thus, the loss of dopaminergic neurons and degeneration should be an area of research focus to identify a therapeutic solution for metabolic change-induced PD. (frontiersin.org)
  • However, it is noteworthy that rat models of Pink1 and DJ-1 loss-of-function showed progressive loss of mDA neurons [8] . (prolekare.cz)
  • Furthermore, when I analysed the Ngn2 knockout mutants, I found that they displayed an early loss of mesDA neurons that was partially maintained at postnatal stages, showing that Ngn2 has a role in the generation of the mesDA neurons. (dissertations.se)
  • These are usually attributed to a psychological reaction to the general motor impairment and to a loss of some of the neurons within the ventral tegmental area (VTA). (inserm.fr)
  • In the present study, we compared the differentiation efficiency of DA neurons from hESCs with and without the application of LIM homeobox transcription factor 1 alpha (LMX1A), a master regulatory protein in the development of the midbrain neurons and SHH proteins. (springer.com)
  • These findings pave the way for enhancing the differentiation of hESCs to DA neurons safely and efficiently without genetic modification. (springer.com)
  • This chapter describes the procedure for the derivation of dopaminergic (DA) neurons from hESCs. (thermofisher.com)
  • After perfusion and sectioning of the implanted rat brains, the number and distribution of Fluoro-Jade and tyrosine hydroxylase-positive neurons were. (lu.se)
  • After perfusion and sectioning of the implanted rat brains, the number and distribution of Fluoro-Jade and tyrosine hydroxylase-positive neurons were evaluated at 6, 10, 14, and 42 days posttransplantation. (lu.se)
  • Since the majority of transplanted tyrosine hydroxylase-positive neurons most probably die before 6 days after transplantation, neuroprotective strategies should primarily focus on the transplantation procedure and the first week after implantation. (lu.se)
  • One gene, Ptf1a, was only expressed in dopaminergic neurons/coronet cells, but not in any other neurons, so we then analyzed it further. (news-medical.net)
  • We then classified the cells expressing Ptf1a into different subgroups and found that those that most completely differentiated into dopaminergic neurons also expressed the gene Meis,' Takeo Horie says. (news-medical.net)
  • Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. (sigmaaldrich.com)
  • The present results provide further evidence for specific and direct effects of PDGF-BB on gene expression, survival and neurite outgrowth of mesencephalic dopaminergic neurons of rat and human origin. (lu.se)
  • Our novel approach directly activates TFs to drive mDA neuron differentiation without relying on cell-extrinsic factors or virus-mediated gene delivery. (kennedykrieger.org)
  • SOCE-associated flight deficits in adult Drosophila derive extensively from regulation of gene expression in pupal neurons, and one such SOCE-regulated gene encodes the small GTPase Ral . (eneuro.org)
  • Differences in the spatiotemporal expression and epistatic gene regulation of the mesodiencephalic dopaminergic precursor marker PITX3 during chicken and mouse development. (semanticscholar.org)
  • The researchers took advantage of this simplicity by performing the sequencing of RNA for single cells across whole embryos, revealing that two molecules, Ptf1a and Meis, are vital for the emergence of dopaminergic neurons/coronet cells, a simple early form of the hypothalamus. (news-medical.net)
  • We were able to sequence the RNA from about 5000 cells from sea squirt embryos and identified the particular neurons that we wished to focus on by finding dopaminergic marker genes in their expression profiles,' corresponding author Yasunori Sasakura says. (news-medical.net)
  • These neurons displayed markers and electrophysiological properties that mirror those of native mature dopamine-producing nerve cells that are normally found in other areas of the brain. (genengnews.com)
  • Initially, I was a little disappointed that we altered the properties of medium spiny neurons and not the supporting glial cells we were targeting," admits Chun-Li Zhang, Ph.D., professor of molecular biology at UT Southwestern Medical Center, and a W.W. Caruth, Jr. scholar in biomedical research. (genengnews.com)
  • Previous work has indicated that while resident glial cells in the mouse brain can be prompted to differentiate into neurons, its always been thought that mature neurons generally can't be reprogrammed. (genengnews.com)
  • In contrast to glial cells that can become reactive and proliferate under certain conditions, postmitotic neurons do not normally change their identity for the lifespan of the organism," the authors write. (genengnews.com)
  • Using this type of approach the team hoped to induce glial cells in the adult mouse brain to differentiate into dopaminergic neurons. (genengnews.com)
  • Further rounds of experiments showed that while the iDALS retained some characteristics of the original cells, they expressed features typical of dopaminergic neurons, demonstrated characteristic electrophysiological properties and spontaneous action potential firing patterns, and formed connections with other neurons. (genengnews.com)
  • This mechanism explains the discrete nature of bursting in dopaminergic cells and demonstrates how synaptic signals may be reshaped by local intrinsic properties of a neuron before influencing action potential generation. (jneurosci.org)
  • but at the cellular level it is not known how dopaminergic cells generate this complex signal. (jneurosci.org)
  • Do dopaminergic cells simply relay a signal generated elsewhere, or do they synthesize its reward-related signal from a diverse set of inputs? (jneurosci.org)
  • We show further that manipulations to increase the activity of cyclic AMP-dependent protein kinase A, which is known to antagonize hedgehog signaling, can block dopaminergic neuron induction by floor plate cells. (nih.gov)
  • These results demonstrate that transplanted ES cells can develop spontaneously into DA neurons. (pnas.org)
  • We show that naive ES cells, when grafted in low numbers, develop into normal midbrain-like DA neurons that reduce motor asymmetries and normalize DA presynaptic markers and down-stream corticostriatal hemodynamic changes in animal models of PD. (pnas.org)
  • Dopaminergic neurons are brain cells whose primary neurotransmitter is dopamine. (sciencephoto.com)
  • Fgf20, which acts on proximal cells, significantly enhanced the survival of cultured dopaminergic neurons by activating the mitogen-activated protein kinase (MAPK) pathway through Fgf receptor 1c. (frontiersin.org)
  • Cell replacement therapy (that is, transplantation of dopaminergic neurons into the brain to replace lost cells and restore function) as proposed in this application attempts to use cells as small pumps of dopamine that will be secreted locally and in a regulated way, and will therefore avoid the complications of other modes of treatment. (ca.gov)
  • Large AIS-positive axon-bearing DA neurons are exclusively produced during early embryonic stages, leaving small anaxonic AIS-negative cells as the only DA subtype generated via adult neurogenesis. (elifesciences.org)
  • Microglia, the primary mediators of neuroinflammation, are innate immune cells of the CNS found in and around degenerating dopaminergic (DA) neurons ( 10 - 12 ). (jimmunol.org)
  • Infiltrating T cells are observed around degenerating DA neurons with activated microglia in PD patients and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models ( 14 - 19 ). (jimmunol.org)
  • Moreover, when hiPS mDA progenitor cells are transplanted into 6-OHDA-lesioned PD rats, they survive long term and many develop into bona fide mDA neurons. (jefferson.edu)
  • In addition to iCell DopaNeurons, CDI's MyCell® process can be applied to develop and manufacture cells from donors with dopaminergic neuron-based diseases. (technologynetworks.com)
  • We're excited that CDI will make these cells widely available for research purposes, enabling researchers to better understand dopaminergic neuron-based diseases and work toward possible patient therapies. (technologynetworks.com)
  • When isolating the Ngn2-expressing cells and their direct descendants by FACS from an Ngn2-GFP-KI mouse, I found that the Ngn2-GFP-positive cell fraction contained dopaminergic neurons, in contrast to Ngn2-GFP-negative cells. (dissertations.se)
  • In the present study, stereological counts of TH-ir striatal neurons in aged and parkinsonian nonhuman primates revealed that GDNF delivered via a lentiviral vector (lenti-) further increased the number of these cells. (epfl.ch)
  • Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells. (semanticscholar.org)
  • iv) The fate of dopaminergic neurons in IPD is determined by the extent of RC dysfunction in these cells. (fnr.lu)
  • Dopaminergic LUHMES cells were used to investigate whether ATP-depletion can be uncoupled from cell death as a downstream event in these fully post-mitotic human neurons. (uni-konstanz.de)
  • A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. (wikipedia.org)
  • Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells of the sensory organs, and they send signals to the spinal cord or brain. (wikipedia.org)
  • Neurons are the primary components of the nervous system, along with the glial cells that give them structural and metabolic support. (wikipedia.org)
  • Many neurons have only one axon, but this axon may-and usually will-undergo extensive branching, enabling communication with many target cells. (wikipedia.org)