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 ...
Dive into the research topics of Human iPSCs derived astrocytes rescue rotenone-induced mitochondrial dysfunction and dopaminergic neurodegeneration in vitro by donating functional mitochondria. Together they form a unique fingerprint. ...
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?
In this item we try to elucidate the mechanisms involved in methamphetamine-induced neurotoxicity, in particular in dopaminergic neurons. ...
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 ...
Monoamines, including dopamine (DA), have been linked to aggression in various species. However, the precise role or roles served by the amine in aggression have been difficult to define because dopaminergic systems influence many behaviors, and all can be altered by changing the function of dopaminergic neurons. In the fruit fly, with the powerful genetic tools available, small subsets of brain cells can be reliably manipulated, offering enormous advantages for exploration of how and where amine neurons fit into the circuits involved with aggression. By combining the GAL4/upstream activating sequence (UAS) binary system with the Flippase (FLP) recombination technique, we were able to restrict the numbers of targeted DA neurons down to a single-cell level. To explore the function of these individual dopaminergic neurons, we inactivated them with the tetanus toxin light chain, a genetically encoded inhibitor of neurotransmitter release, or activated them with dTrpA1, a temperature-sensitive ...
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
Tobacco smoking is a public health problem, with ∼5 million deaths per year, representing a heavy burden for many countries. No effective therapeutic
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 ...

No data available that match "dopaminergic neurons"


Dopaminergic neurons -- RDoC Element. Type of Element: Cell. The following construct(s)/subconstruct(s) refer to this element ...
... resulting in an ipsilateral loss of striatal dopamine and of dopaminergic perikarya. A concomitant reduction of displaceable ... Autoradiographic evidence for nicotine receptors on nigrostriatal and mesolimbic dopaminergic neurons Brain Res. 1985 Dec 2;348 ... Thus, nicotine receptors appear to be located on nigrostriatal and mesolimbic dopaminergic neurons at the level of perikarya ... resulting in an ipsilateral loss of striatal dopamine and of dopaminergic perikarya. A concomitant reduction of displaceable ...
... and are in physical contact with tuberoinfundibular dopaminergic (TIDA) neurons, which inhibit prolactin secretion. Prolactin ... Kisspeptin neurons in the arcuate nucleus (ARC) regulate prolactin secretion, ... Interactions between Kisspeptin Neurons and Hypothalamic Tuberoinfundibular Dopaminergic Neurons in Aged Female Rats Acta ... These results suggest that the contacts between TIDA neurons and kisspeptin neurons are maintained after reproductive ...
Role of supraspinal dopaminergic neurons during maturation of zebrafish motor behaviour Author: Ramadhan, Raad ISNI: 0000 0004 ... Studies of both developing and adult zebrafish suggest a role for dopaminergic (DAergic) neurons in regulating spinal motor ... knockdown of D4 receptors or ablation of diencephalon DAergic neurons (DDNs) markedly alters the frequency of immature forms of ... supraspinal dopaminergic neurons ; zebrafish motor behaviour ; Thesis ...
The cells were assigned to 3 groups: (1) control: primary cultured neurons; (2) 6-OHDA: primary cultured neurons and 6-OHDA; ... Topiramate was shown to provide protection to dopaminergic neurons exposed to 6-OHDA by reducing cell apoptosis and enhancing ... the morphology and development of dopaminergic neurons was observed. Hoechst33258 and propidium iodide (PI) double staining was ... Compared with the 6-OHDA group, there were more neurons with greater cell viability in the 6-OHDA plus TPM group.Conclusions: ...
"Dopaminergic Neurons" by people in this website by year, and whether "Dopaminergic Neurons" was a major or minor topic of these ... "Dopaminergic Neurons" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "Dopaminergic Neurons" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Dopaminergic Neurons". ...
... is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways ... Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates Gaia Faustini 1 , Francesca Longhena 1 , Alessia Muscò 1 ... Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates Gaia Faustini et al. Cells. 2022. . ... wt untreated neurons, ** p , 0.01, Syn III ko vs. wt DA-treated neurons, one-way ANOVA + Newman-Keuls). (K,L) The treatment of ...
Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons ... Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha- ... Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons ... "Occurrence of Neuronal Inclusions Combined With Increased Nigral Expression of Alpha-synuclein Within Dopaminergic Neurons ...
A key feature of Parkinsons disease is the dopaminergic neuronal cell loss in the substantia nigra pars compacta. Besides ... Colchicine Protects Dopaminergic Neurons in a Rat Model of Parkinsons Disease. Author(s): Mohamed Salama, Amr Ellaithy, Basem ... Keywords: Colchicine, Parkinsons disease, neuroprotection, anti-apoptotic, rotenone, dopaminergic neurons, efflux system, anti ... Keywords: Colchicine, Parkinsons disease, neuroprotection, anti-apoptotic, rotenone, dopaminergic neurons, efflux system, anti ...
Long-range synaptic and local receptor-mediated control of dopaminergic neuron excitability - dendrites, soma and axons ... NIH Directors Seminar: Long-range synaptic and local receptor-mediated control of dopaminergic neuron excitability - dendrites ...
We tested integration of inhibitory synaptic inputs onto SNc neurons from genetically defined populations in dorsal striatum ( ... dopaminergic neurons respond to aversive stimuli with inhibitory pauses in firing followed by transient rebound activation. ... Functional Dissection of Basal Ganglia Inhibitory Inputs onto Substantia Nigra Dopaminergic Neurons Rebekah C Evans 1 , Emily L ... Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates. Faustini G, Longhena F, Muscò A, Bono F, Parrella E, La ...
Uncovering Molecular Cascades Involved in Midbrain Dopaminergic Neuron Specification. *Awatramani, Rajeshwar (PD/PI) ...
Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017). VTA neurons: ... A dopaminergic (DA) neuron model with a morphologicaly realistic dendritic architecture. The model captures several salient ... Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017) ... Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017) ...
Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017). VTA neurons: ... A dopaminergic (DA) neuron model with a morphologicaly realistic dendritic architecture. The model captures several salient ... Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017) ... Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017) ...
This work thus identifies for the first time a population of dopaminergic neurons that regulates motor behavior capable of ... Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers After Cell ... Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers After Cell ... Title : Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers After ...
BookRole of glutamate N-Methyl-D-Aspartate receptor surface trafficking in the firing pattern of midbrain dopaminergic neurons ... Résumé / Abstract : Midbrain dopaminergic (DA) neurons play several key functions in the brain such as the processing of ... Role of glutamate N-Methyl-D-Aspartate receptor surface trafficking in the firing pattern of midbrain dopaminergic neurons / ... Because these processes have in common to modify the firing activity of midbrain DA neurons, it is of crucial importance to ...
Functionality of spines and filopodia-like processes located on dendrites of midbrain dopaminergic neurons. Friday, September ... In midbrain dopamine neurons, anatomical evidence for the presence of dendritic spines has been mixed with some studies ... Here, we report that dendritic spines of highly variable length were present on dopamine neurons visualized in live slices as ... observing the presence of spine-like processes while others concluding that dopamine neurons are largely aspiny. Furthermore, ...
In this study, we determined the extent to which 27-OHC regulates α-syn levels in human dopaminergic neurons, the cell type in ... Human primary dopaminergic neuronal precursor cells were cultured and differentiated into human dopaminergic neurons according ... Human dopaminergic neurons express Tyrosine Hydroxylase. Bright field microscopy of human dopaminergic neuronal precursor cells ... suggesting that these neurons are predominantly of dopaminergic origin. (D) is immunostaining with the neuron specific β-III ...
Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. Minae Niwa, Hanna Jaaro-Peled, ... In a mouse model of this phenomenon, a mild isolation stress affects the mesocortical projection of dopaminergic neurons in ... Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. / Niwa, Minae; Jaaro-Peled, Hanna; ... In a mouse model of this phenomenon, a mild isolation stress affects the mesocortical projection of dopaminergic neurons in ...
Tag Archive for: Dopaminergic Neurons. You are here: Home1 / Dopaminergic Neurons ... Here we report that CB2Rs are expressed in ventral tegmental area (VTA) DA neurons and functi… ...
BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature, Vol. 350. pp. 230-232. ... 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 ... A protein partially purified from bovine striatum, a target of nigral dopaminergic neurons, with characteristics apparently ...
Dopaminergic Neuron Induction Mechanisms The success of emerging CRT for PD will depend on other issues, such as the ... These studies have suggested that approximately 100,000 dopaminergic neurons need to be present within the grafted striatum to ... it was demonstrated by several clinical studies performed in the 1990s that replacement of lost dopaminergic neurons in the ... Moreover, mutant Wnt mice showed a loss of most midbrain DA neurons and ectopic expression of Wnt-1 and -5a in NSCs lead to DA ...
... dopaminergic neurons at 4 weeks, DA6W: Dopaminergic neurons at 6 weeks). (E,G) Bar charts showing the average expression levels ... Chen, E. S., Lauinger, N., Rocha, C., Rao, T. & Durcan, T. M. Generation of dopaminergic or cortical neurons from neuronal ... Generation of cortical and dopaminergic neurons. The induction of cortical progenitors was performed as described previously25 ... DA-NPCs were subsequently differentiated into dopaminergic neurons (DANs), with immunostaining and qPCR analysis performed at ...
The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA. Neuron. 2010 Nov 18; ... The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA. In: Neuron. 2010 ; ... The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA. Neuron, 68(4), 682- ... The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA, Neuron, vol. 68, no ...
The inhibition of porin in dopaminergic neurons among others result in reduced lifespan and age-dependent loss in climbing ... This enhancement of the α-synuclein-induced phenotypes observed in neurons was demonstrated in the neuron rich eye, where the ... The UAS/Gal4 expression system was exploited with directed expression in neurons achieved with the use of the Dopa ... The expression of α-synuclein in neuronal populations that include dopamine producing neurons under the control of Ddc-Gal4 ...
Development and activity-dependent plasticity of olfactory bulb dopaminergic neurons. Add to your list(s) Download to your ... Development and activity-dependent plasticity of olfactory bulb dopaminergic neurons ...
... ... which arises as a result of the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra. The severity ... With regard to PD, it would be interesting to know if these neurons have differentiated toward a midbrain or even mDA neuronal ... Rat ES cells have been reported to differentiate into neurons by means of adjusting the level of MEK/ERK inhibition. ...
Dopaminergic neurons projecting to M1 are located in VTA. For the hemisphere analyzed, 48% of TH-positive midbrain neurons were ... Retrograde tracing identified dopaminergic neurons in VTA that projected to M1. A small number of these neurons was also found ... Destroying dopaminergic neurons in VTA depletes M1 of dopaminergic terminals and prevents motor skill learning. Considering the ... 1982) The organization of dopaminergic and non-dopaminergic mesencephalo-cortical neurons in the rat. Brain Res 238:421-425. ...
  • Parkinson's disease is characterized by the progressive loss of dopaminergic neurons - neurons that communicate by releasing a major chemical messenger in the brain called dopamine. (infinitenest.org)
  • KEY RESULTS: Both pioglitazone and GW855266X protected against 6-OHDA induced loss of dopaminergic neurons in the substantia nigra and depletion of striatal dopamine when administered orally twice daily for either 1) 7 day prior to and 7 days post lesioning or 2) for 7 days starting 2 days post lesioning when neurons will be severely traumatized. (ox.ac.uk)
  • Most PD medications currently available relieve motor symptoms, compensatingfor the loss of dopaminergic neurons. (neuramedy.com)
  • Parkinson's disease (PD) might be a mutual neurodegenerative disease considered by a movement disorder containing rest tremor, bradykinesia, rigidity, and postural instability, and second-leading reason of dementia and is categorized by an advanced loss of dopaminergic neurons within the neural structure alongside the occurrence of intraneuronal α-synuclein-positive enclosures. (stmjournals.in)
  • We conclude that both the asymmetric terminal and symmetric en passant synapses take origin from a single nigrostriatal dopaminergic neuronal population and that dopaminergic transmitter markers occur only in one of these synaptic types in the rat striatum. (nih.gov)
  • Attention deficit and hyperactivity disorder ( ADHD ) is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways. (bvsalud.org)
  • In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson's disease or multiple system atrophy. (ox.ac.uk)
  • Identification of bioactive metabolites in human iPSC-derived dopaminergic neurons with PARK2 mutation: Altered mitochondrial and energy metabolism. (ox.ac.uk)
  • Progressive degeneration of dopaminergic (DA) neurons in the substantia nigra is a hallmark of Parkinson's disease (PD). (nature.com)
  • The progressive and selective degeneration of mDA neurons in the substantia nigra (SN) reduces nigrostriatal DA transmission, leading to the motor symptoms of Parkinson's disease (PD). (nature.com)
  • The present study examined whether crosstalk between cannabinoid (CB) and transient potential receptor vanilloid type 1 (TRPV1) could contribute to the survival of nigrostriatal dopamine neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). (hindawi.com)
  • Parkinson's disease (PD) is a well-known neurodegenerative disorder that is characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta (SNpc) and dopamine deficiency in the striatum (STR), consequently resulting in motor dysfunction [ 1 , 2 ]. (hindawi.com)
  • 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. (tsukuba.ac.jp)
  • The guidance cues to be tested regulate the orientation the axons (communication cables) of developing and regenerating neurons, which controls neural network formation, necessary for stem cell therapy to benefit patients with Parkinson's disease. (dana.org)
  • Parkinson's disease progressively depletes neurons that use the transmitter dopamine to communicate with one anther. (dana.org)
  • If improper activation of one or both signals occurs, this information will help to identify the proteins that are necessary to effectively guide the axons of stem cell-derived neurons to their appropriate targets in Parkinson's disease. (dana.org)
  • Parkinson's disease (PD) is a progressively debilitating neurological disorder that results from the loss of dopaminergic (DA) neurons of the ventral midbrain. (dana.org)
  • Phenotypic manifestation of α-synuclein strains derived from Parkinson's disease and multiple system atrophy in human dopaminergic neurons. (ox.ac.uk)
  • α-Synuclein is critical in the pathogenesis of Parkinson's disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. (ox.ac.uk)
  • Our study demonstrates how Parkinson's disease-associated genes influence the phenotypic manifestation of strains in human neurons. (ox.ac.uk)
  • Researchers have devised a new method to generate dopamine-producing neurons from skin cells of Parkinson's disease patients, a process that could be used to better study the molecular mechanisms of the disease and develop new treatments. (infinitenest.org)
  • Using the new method, the researchers generated dopaminergic neurons from 18 Parkinson's patients, and 10 age- and sex-matched healthy controls. (infinitenest.org)
  • Compared with healthy controls, neurons from Parkinson's patients had impaired stress-induced autophagy, a natural recycling process in which cells degrade unnecessary or damaged components. (infinitenest.org)
  • Notably, neurons obtained from both healthy and Parkinson's disease patients exhibited characteristics related to the age of the patient. (infinitenest.org)
  • Ventral midbrain (VM) dopaminergic (DA) neurons, which project to the dorsal striatum via the nigrostriatal pathway, are progressively degenerated in Parkinson's disease (PD). (ucc.ie)
  • Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. (elsevier.com)
  • Neural grafting techniques may have clinical application in the treatment of Parkinson's disease, and a single graft can cause significant behavioral recovery in rodent models of striatal dopaminergic denervation. (elsevier.com)
  • Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease. (omicsdi.org)
  • Recent reports have indicated human embryonic stem cells-derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. (omicsdi.org)
  • Illustration of Parkinson's disease which makes the brain gradually loosing dopaminergic neurons like a tree its leaves. (unibas.ch)
  • Preclinical evaluation of the therapeutic potential of dopamine (DA) neuron alternative in Parkinson's illness (PD) has primarily been carried out in the 6-hydroxydopamine toxin model. (g2reports.com)
  • Parkinson's disease (PD) is a neurodegenerative disorder, affectingmotor and non-motor functions of the central and peripheral nervous systems, including the dopaminergic neurons of the substantia nigra.The incidence of PD is one of the highest among all neurological disorders. (neuramedy.com)
  • Tauroursodeoxycholic acid prevents MPTP-induced dopaminergic cell death in a mouse model of Parkinson's disease. (wehaveparkinsons.com)
  • Parkinson's disease is thought to be a progressive neurodegenerative disorder where the dopaminergic neurons of the substantia nigra part of the brain are destroyed. (naturalpathhealthcenter.com)
  • Our data demonstrate that chronic stimulation of DA D2 receptors does not impair survival or differentiation of cultured fetal dopaminergic neurons. (vumc.nl)
  • Two related members of the bone morphogenetic protein (BMP) family, BMP2 and growth/differentiation factor (GDF) 5, which signal via a canonical Smad 1/5/8 signalling pathway, have been shown to have neurotrophic effects on midbrain DA neurons both in vitro and in vivo, and may function to regulate VM DA neuronal development. (ucc.ie)
  • Taken together, these experiments identify GDF5 and BMP2 as novel regulators of midbrain DA neuronal induction and differentiation, and demonstrate that their effects on DA neurons are mediated by canonical BMPR-Smad signalling. (ucc.ie)
  • Our proprietary transcription factor-based stem cell differentiation method produces neurons without a genetic footprint. (elixirgensci.com)
  • Midbrain Cues Dictate Differentiation of Human Dental Pulp Stem Cells Towards Functional Dopaminergic Neurons. (manipal.edu)
  • 2011) Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells. (jenabioscience.com)
  • Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell. (omicsdi.org)
  • mouse embryonic stem cells (mESCs) and protein-based iPS cells (P-iPSCs) generated by non-viral methods, into midbrain dopaminergic (mDA) neurons, and then compared the efficiency of DA neuron differentiation from these two cell types. (omicsdi.org)
  • Here, we transplanted three types of mDA cells, DA progenitors (differentiated in vitro for 16 days [D16]), immature DA neurons (D25), and DA neurons (D35), into PD mice and found that all three types of cells showed high viability and strong neuronal differentiation in vivo. (omicsdi.org)
  • Additionally, we found de novo DNA methylation during in vitro differentiation for hundreds of genes specifically in lineage-committed neural precursors that persisted in iPSC-derived DA neurons. (omicsdi.org)
  • In contrast, fine structural immunohistochemical studies with antibodies to tyrosine hydroxylase and dopamine have consistently labeled primarily symmetric synapses en passant within the striatum. (nih.gov)
  • Thus, we suggest that single dopaminergic neurons in the substantia nigra make two types of synaptic contact with striatal cells: 1) symmetric synapses en passant, which can be stained with tyrosine hydroxylase and dopamine and which contact dendritic spine necks, and 2) asymmetric terminal boutons of unknown chemical nature which end on dendritic spine heads. (nih.gov)
  • MPTP induced a significant loss of nigrostriatal dopamine neurons and glial activation in the substantia nigra (SN) and striatum (STR) as visualized by tyrosine hydroxylase (TH) or macrophage antigen complex-1 (MAC-1) or glial fibrillary acidic protein (GFAP) immunocytochemistry, respectively. (hindawi.com)
  • To complete this study, we will use novel fluorescence biosensors to visualize in live developing neurons tyrosine phosphorylation and Cdc42 activity. (dana.org)
  • In Aim 1, we will examine whether localized changes in tyrosine phosphorylation and Cdc42 activity correlate with chemotropic turning of growth cones of primary embryonic neurons in gradients of Netrin and Slit. (dana.org)
  • We used tyrosine hydroxylase (TH) immunoreactivity (ir) to ensure that the neurons detected synthesize DA endogenously. (umn.edu)
  • Cultured dopaminergic neurons, as visualized by tyrosine hydroxylase immunocytochemistry, became more differentiated in the course of cultivation time and exhibited specific high-affinity uptake for [3H]DA. (vumc.nl)
  • Daily treatment of these cultures for 7 days with LY 171555 or sulpiride did not lead to any change in protein content, the number of tyrosine hydroxylase-immunoreactive neurons, or the uptake capacity for [3H]DA. (vumc.nl)
  • Nigral tyrosine hydroxylase (TH)-positive neurons as well as oxidative markers 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE) and striatal dopamine levels were quantified for assessment of the neuroprotective efficacy of diapocynin. (springer.com)
  • Immunofluorescence and flow cytometry analysis showed enhanced expression of mature neuronal marker Map2ab and dopaminergic-neuronal markers [tyrosine hydroxylase (TH), En1, Nurr1 and Pitx3], with nearly 77% of the induced DPSCs positive for TH. (manipal.edu)
  • The transcription factor REST up-regulates tyrosine hydroxylase and antiapoptotic genes and protects dopaminergic neurons against manganese toxicity. (meharryresearch.org)
  • Then, brain of the animals was perfused to assess survival of dopaminergic (DAergic) neurons in substantia nigra by tyrosine hydroxylase (TH) immunohistochemistry. (bvsalud.org)
  • Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential (AP) and a biphasic postinhibitory response. (univ-amu.fr)
  • Primary cultures of rat ventral mesencephalon were used to elucidate the role of chronic stimulation of dopamine (DA) D2 autoreceptors in the development of fetal dopaminergic neurons in vitro. (vumc.nl)
  • We find that dopaminergic neurons in vitro establish a distinctive axonal arbor compared to glutamatergic or GABAergic neurons in both size and propensity of terminals to avoid direct contact with target neurons. (ulaval.ca)
  • IPSC-derived mDA neuron-like cells have been generated, however, detailed genetic and epigenetic characterization of strictly purified in vitro generated DA neurons has so far lagged behind. (omicsdi.org)
  • ABSTRACT: Burst firing of dopaminergic neurons of the substantia nigra pars compacta can be induced in vitro by the glutamate agonist N-methyl-D-aspartate. (physiomeproject.org)
  • In this study we investigated human pluripotent stem cells (hPSC) and different neural progenitor states to characterize the expression of the plasma membrane calcium ATPases (PMCAs) during human neural development and in mature mesencephalic dopaminergic (mesDA) neurons. (frontiersin.org)
  • Here, by studying zebrafish embryos exposed to Syn III gene knock-down (KD), Syn III knock-out (ko) mice and human induced pluripotent stem cells (iPSCs)-derived neurons subjected to Syn III RNA interference , we found that Syn III governs the earliest stages of dopaminergic neurons development and that this function is conserved in vertebrates . (bvsalud.org)
  • Quick-Neuron™ Dopaminergic - mRNA Kit This kit differentiates human pluripotent stem cells into dopaminergic neurons in 10 days using synthetic mRNA. (elixirgensci.com)
  • Midbrain dopaminergic (mDA) neurons derived from pluripotent stem cells are of substantial interest because of their instrumental value for PD therapy. (omicsdi.org)
  • Recent evidence suggests that glial cell activation and its inflammatory response may contribute to the progressive degeneration of dopaminergic neurons in PD. (springer.com)
  • To determine whether PDF+ neurons synapse with dopaminergic axons, Potdar and Vasu used a GFP reconstitution across synaptic partners (GRASP) experiment. (eneuro.org)
  • When the two GFP fragments were expressed in PDF+ and dopaminergic neurons, staining with an anti-GFP antibody revealed colocalization in the ascending portion of small lateral ventral neuron (s-LNv) dorsal projections, confirming synaptic connections ( Fig. 1 ). (eneuro.org)
  • The membrane properties and the synaptic control of the neurons in the lamprey basal ganglia output stages are investigated and electrophysiological and immunohistochemical studies to investigate morphology and physiology properties are combined. (semanticscholar.org)
  • Paired whole-cell recordings are used to show that inhibitory synaptic potentials generated from single interneurons are sufficiently powerful to delay or entirely block the generation of action potentials in a large number of projection neurons simultaneously. (semanticscholar.org)
  • Dopaminergic neurons establish a distinctive axonal arbor with a majority of non-synaptic terminals. (ulaval.ca)
  • While most dopaminergic varicosities are active and contain exocytosis proteins like synaptotagmin 1, only ~20% of these are synaptic. (ulaval.ca)
  • 2019. Isoflurane Inhibits Dopaminergic Synaptic Vesicle Exocytosis Coupled to Ca2.1 and Ca2.2 in Rat Midbrain Neurons. . (cornell.edu)
  • When an electric current "fires" across the surface of a neuron, it causes some of the vesicles to migrate to the synapses and release their NT contents into the synaptic gap [see Figure 1]. (antiaging-nutrition.com)
  • TRPV1 is widely present in various neurons and glial cells (microglia and astrocytes) in the nigrostriatal pathway in vivo [ 10 - 12 ]. (hindawi.com)
  • In adult retinas, microglia maintain the normal structure and function of neurons and other glial cells, but the mechanism underlying this process is not well-understood. (researchgate.net)
  • Neuron-derived alpha-synuclein also reacts with TLR2 on neighboring glial cells,resulting in inflammation ofthe brain parenchyma. (neuramedy.com)
  • Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. (ox.ac.uk)
  • Here, we investigated association between dopaminergic neuronal death, as the main pathophysiological mechanism underlying PD, and serum levels of glucose, FFA and IL-1ß in 6-hydroxydopamine (6-OHDA) animal model of PD. (bvsalud.org)
  • The human brain is exceedingly complex, consisting of various regions with particular functions and approximately 100 billion neurons. (tsukuba.ac.jp)
  • In a new study reported in Genes and Development , a research team centered at University of Tsukuba has developed a novel approach for revealing how the brain forms via the creation of different types of neurons using a sea squirt, a simple organism that is a precursor to the vertebrates. (tsukuba.ac.jp)
  • The sea squirt is a useful model for studying brain development as it presents some basic features of all vertebrates at an early evolutionary stage, while having a central nervous system containing only 177 neurons. (tsukuba.ac.jp)
  • Kappa opioid receptor-mediated regulation of dopaminergic neurons in the rat brain. (aspetjournals.org)
  • In addition, we found a novel dopaminergic cluster, C4, located above the dorsomedial border of the lobula, which innervates the visual neuropils of the bee brain. (umn.edu)
  • The profuse dopaminergic innervation of the entire bee brain and the specific connectivity of DA neurons, with visual, olfactory and gustatory circuits, provide a foundation for a deeper understanding of how these sensory modules are modulated by DA, and the DA-dependent value-based associations that occur during associative learning. (umn.edu)
  • Here we selectively activated THVTA neurons in transgenic rats and measured resulting changes in whole-brain activity using stimulus-evoked functional magnetic resonance imaging. (elsevier.com)
  • However, brain-wide voxel-based principal component analysis of the same data set revealed that dopaminergic modulation activates several additional anatomically distinct regions throughout the brain, not typically associated with dopamine release events. (elsevier.com)
  • These data suggest that modulation of THVTA neurons can impact brain dynamics across many distributed anatomically distinct regions, even those that receive little to no direct THVTA input. (elsevier.com)
  • Brain tissue was fixed following α-synuclein overexpression for immunofluorescence studies of dopaminergic neurons which were quantified by the HALO image analysis platform . (indicalab.com)
  • Pech U, Pooryasin A, Birman S, Fiala A (2013): Localization of the contacts between Kenyon cells and aminergic neurons in the Drosophila melanogaster brain using splitGFP reconstitution. (uni-goettingen.de)
  • It is a chronic and progressive disease that affects the dopaminergic neurons in a specific area of the brain, called the substantia nigra (6,7). (who.int)
  • The brain alone is made up of tens of millions of neurons, of which there are several types, as well as numerous other cell types, such as glia, oligodendrocytes, and astrocytes. (labiotech.eu)
  • A typical brain has roughly 100 billion neurons. (unist.ac.kr)
  • Excitotoxins are biochemical substances (usually amino acids, amino acid analogs, or amino acid derivatives) that can react with specialized neuronal receptors - GLU receptors - in the brain or spinal cord in such a way as to cause injury or death to a wide variety of neurons (1-3, 8-10). (antiaging-nutrition.com)
  • Our studies show that alterations of dopaminergic signaling in the brain affects liver metabolism in a circadian manner. (yidashuzi.com)
  • These results highlight the important connectivity between single type of neurons and metabolism and show how psychoactive drugs impact physiology through direct brain-liver connections," says Emiliana Borrelli, PhD, professor of Microbiology & Molecular Genetics at UCI School of Medicine, who, for this study, collaborated with the late Paolo Sassone-Corsi, PhD, professor of Biological Chemistry at UCI. (yidashuzi.com)
  • Going beyond current studies on substance use disorders, which focus on the impact of addictive drugs on the brain, this new research highlights an existing connection between specific neurons and peripheral organs. (yidashuzi.com)
  • These results uncover a strict communication between neurons/brain areas and liver metabolism as well as the association between substance use and systemic deficits," said Borrelli. (yidashuzi.com)
  • Pitolisant is an H3 receptor antagonist/inverse agonist mediated at the presynaptic level through the activation of histaminergic neurons in the brain. (medscape.com)
  • Researchers will use "fluorescence imaging biosensors" to visualize biochemical signals within neurons derived from embryonic stem cells to test whether these neurons respond appropriately to molecular guidance cues. (dana.org)
  • For cell therapy to succeed, new DA neurons derived from embryonic stem cells (ESC) must respond appropriately to extracellular guidance information. (dana.org)
  • However, a recent study using dopaminergic neurons derived from embryonic stem cells found that these neurons do not respond to chemotropic gradients of Netrin or Slit. (dana.org)
  • In Aim 2, we will perform similar experiments using dopaminergic neurons derived from mouse embryonic stem cells. (dana.org)
  • This chapter demonstrates that mesencephalic tissue from embryonic porcine litters provides a viable source of dopaminergic tissue that is appropriately integrated into the chronically immunosuppressed rat host. (elsevier.com)
  • The results demonstrate that xenografts of embryonic porcine dopaminergic neurons survive, when transplanted into chronically immunosuppressed hosts from a widely divergent phylogenetic order. (elsevier.com)
  • Our data clearly demonstrates for the first time that DPSCs in the presence of embryonic midbrain cues show efficient propensity towards functional dopaminergic cell-type. (manipal.edu)
  • Current experimental studies, such as the development of neuroprotective agents on dopamine neurons through regulating glial activation and preventing production of neurotoxic inflammatory molecules, have provided opportunities to develop innovative strategies for PD therapy [ 5 ]. (hindawi.com)
  • Given that more than 95% of the nigrostriatal projection arises from dopamine fluorescent neurons, it would appear that both the asymmetric and symmetric terminals belong to the same type of neuron. (nih.gov)
  • If a particular type of neuron, or astrocytes, or microglia cannot be produced, then the disease cannot be studied. (labiotech.eu)
  • Key findings for PARK2 KO cells were confirmed using patient-specific iPSC-derived neurons. (ox.ac.uk)
  • Quick-Neuron™ Dopaminergic - Human iPSC-derived Neurons display typical neurite outgrowth and express a variety of neuronal markers, such as TUBB3 (pan-neuronal) and TH (dopaminergic). (elixirgensci.com)
  • When thawed and maintained according to the instructions in the user guide, the iPSC-derived neurons are viable long-term and are suitable for a variety of characterization and neurotoxicity assays. (elixirgensci.com)
  • Researchers have been experimenting with stem cell therapy to determine whether the stem cell-derived neurons can effectively be reincorporated into the correct neural networks. (dana.org)
  • Thus, our results suggest that changes in dopamine signaling in specific striatal neurons evoke major changes in liver physiology. (yidashuzi.com)
  • Indeed, the metabolic disturbances observed between normal mice and those with an impaired dopamine D2 receptor signaling in striatal medium spiny neurons is greatly enhanced by cocaine, a substance of abuse and psychomotor stimulant, as shown in the pie charts. (yidashuzi.com)
  • By analyzing the liver metabolome of mice deficient in the expression of the dopamine D2 receptor (D2R) in striatal medium spiny neurons, the researchers found profound changes in the liver circadian metabolome compared to control mice. (yidashuzi.com)
  • D2R signaling in medium spiny neurons is key for striatal output and is essential for regulating the first response to the cellular and rewarding effects of cocaine," said Borrelli. (yidashuzi.com)
  • This study shows that dopamine D2 receptors (D2R) in striatal medium spiny neurons (MSNs) play a key role in regulating diurnal liver metabolic activities. (yidashuzi.com)
  • Drosophila Fer2 is a prime example of a developmental transcription factor required for the birth and maintenance of midbrain DA neurons. (nature.com)
  • Our results reveal the essential and conserved role of Fer 2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modeling and treating PD. (nature.com)
  • By activating, modulating and/or inhibiting various components of the BMP-Smad signalling pathway, this research demonstrated that GDF5- and BMP2-induced neurite outgrowth from midbrain DA neurons is dependent on BMP type I receptor activation of the Smad signalling pathway. (ucc.ie)
  • ZIGMOND, M.J. Evidence for two functionally distinct subpopulations of neurons within the striatum and their differential sensitivity to dopamine. (bvsalud.org)
  • Two extracellular factors that guide fetal DA neurons are Netrin and Slit. (dana.org)
  • We further show that conditional ablation of Nato3 , a mouse homolog of Fer2 , in differentiated DA neurons causes mitochondrial abnormalities and locomotor impairments in aged mice. (nature.com)
  • By contrast, treatment with capsaicin (a specific TRPV1 agonist) increased the survival of dopamine neurons in the SN and their fibers and dopamine levels in the STR in MPTP mice. (hindawi.com)
  • Moreover, treatment with anandamide (an endogenous agonist for both CB and TRVP1) rescued nigrostriatal dopamine neurons and reduced gliosis-derived neuroinflammatory responses in MPTP mice. (hindawi.com)
  • However, to the best of our knowledge, marked alterations in biochemical and morphological setup of midbrain dopaminergic pathways by gintonin in MPTP mice model have not been previously reported. (elsevier.com)
  • Isoflurane Modulates Hippocampal Cornu Ammonis Pyramidal Neuron Excitability by Inhibition of Both Transient and Persistent Sodium Currents in Mice. (cornell.edu)
  • Isoflurane Suppresses Hippocampal High-frequency Ripples by Differentially Modulating Pyramidal Neurons and Interneurons in Mice. (cornell.edu)
  • IMSEAR at SEARO: Dose-dependent response of central dopaminergic systems to metoclopramide in mice. (who.int)
  • The interaction between cortical and dopaminergic inputs to CD neurons may underlie the behavioral adaptation toward purposeful saccades, which reflects working memory, expectation, and attention. (semanticscholar.org)
  • Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content. (cocites.com)
  • This is the result of the spontaneously occurring wave oscillations that account for the intracellular recordings from thalamic and cortical neurons. (alchetron.com)
  • 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. (tsukuba.ac.jp)
  • 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. (tsukuba.ac.jp)
  • One gene, Ptf1a , was only expressed in dopaminergic neurons/coronet cells, but not in any other neurons, so we then analyzed it further. (tsukuba.ac.jp)
  • 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. (tsukuba.ac.jp)
  • They will use fluorescence imaging to determine whether two key biochemical signals are activated normally within dopaminergic neurons derived from stem cells. (dana.org)
  • Now, a team led by researchers in Sweden devised a way to generate dopaminergic neurons from skin cells directly, without going through the stem cell intermediate. (infinitenest.org)
  • The nerve cells were obtained by treating skin cells with an optimal combination of factors required for the normal development and function of dopaminergic neurons. (infinitenest.org)
  • Analyses of the resulting cells showed they were behaving like neurons - they could spontaneously fire electrical signals - and had increased activity of genes related to dopamine, therefore determining the validity of the model. (infinitenest.org)
  • These defects were not observed in the skin cells before they were converted into neurons, confirming that disease features are observed only in neurons. (infinitenest.org)
  • Moreover, in neurons derived from skin cells, they detected alpha-synuclein pathology, but not in the neurons derived from iPSC. (infinitenest.org)
  • Such an understanding would facilitate the generation of transplantable DA neurons from stem cells and the identification of developmentally-relevant neurotrophic factors, the two most promising therapeutic approaches for PD. (ucc.ie)
  • Several reports have demonstrated the activation of microglial cells and astroglial cells in close proximity to the damaged or dying dopaminergic neurons in SN [ 5 ]. (springer.com)
  • Ganglion cells are the projection neurons of the retina. (researchgate.net)
  • While both stem cell types were differentiated to the terminally-matured mDA neurons, P-iPSCs showed higher DA neuron-specific markers' expression than ES cells. (omicsdi.org)
  • To investigate the mechanism of the superior induction capacity of DA neurons observed in P-iPSCs compared to ES cells, we analyzed histone modifications by genome-wide ChIP sequencing analysis and their corresponding microarray results between two cell types. (omicsdi.org)
  • Using an approach combining ChIP-seq, RNA-seq, and genetic epistasis experiments with PD-linked genes, here we demonstrate that Fer2 controls a transcriptional network to maintain mitochondrial structure and function, and thus confers dopaminergic neuroprotection against genetic and oxidative insults. (nature.com)
  • However, most gene expression patterns of iPSC-derived DA neurons closely resembled that of primary mdDA neurons with the strongest correlations for mdDA specific genes. (omicsdi.org)
  • Gene expression of genes in the dopaminergic pathway will be affected by GenX and ADONA. (cdc.gov)
  • 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. (tsukuba.ac.jp)
  • The major neuronal type within the NAc is the GABAergic medium spiny neuron (MSN), whose activity is regulated by dopaminergic inputs. (nih.gov)
  • Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. (elsevier.com)
  • In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity. (elsevier.com)
  • Full and partial peroxisome proliferation-activated receptor-γ agonists, but not δ agonist, rescue of dopaminergic neurons in the 6-OHDA parkinsonian model is associated with inhibition of microglial activation and MMP expression. (ox.ac.uk)
  • The first section of the wave signifies a down state, which is an inhibition period in which the neurons in the neocortex are silent. (alchetron.com)
  • The researchers hypothesize that modulation of specific signaling pathways must occur with precise spatial and temporal control, as occurs in developing neurons. (dana.org)
  • Dynamical Approaches to understanding cholinergic control of nicotine action pathways in the dopaminergic reward circuits. (ens.fr)
  • Sociosexual investigation in sexually experienced, hormonally manipulated male leopard geckos: relation with phosphorylated DARPP-32 in dopaminergic pathways. (cornell.edu)
  • One promising treatment of PD patients is stem cell therapy, which requires the integration of new DA neurons into existing circuits. (dana.org)
  • In addition, they found that activation of dopaminergic circuits by acute cocaine administration reprograms the circadian liver metabolome. (yidashuzi.com)
  • Survival of dopaminergic (DAergic) neurons in substantia nigra was assessed by immunohistochemistry. (bvsalud.org)
  • Our analyses showed that these two transcription factors work in tandem to stimulate production of these neurons, which also has important implications for how the hypothalamus forms in humans. (tsukuba.ac.jp)
  • However, further analyses showed that decreasing PDFR signaling to dopaminergic neurons increased day-time sleep, whereas increasing PDFR signaling to dopaminergic neurons suppressed day-time sleep and made it fragmented, in addition to delaying sleep onset. (eneuro.org)
  • Previous studies have shown that anterograde transport of tritiated labeled proteins from the substantia nigra to the striatum over short survival times primarily labels asymmetric synapses (and that these asymmetric synapses are preferentially vulnerable to selective dopaminergic neurotoxins such as 6-hydroxydopamine). (nih.gov)
  • Applying a standard generalized linear model analysis approach, our results indicate that selective optogenetic stimulation of THVTA neurons enhanced cerebral blood volume signals in striatal target regions in a dopamine receptor-dependent manner. (elsevier.com)
  • Themain pathological traitsof PD are as follows:(1) selective loss of certain neurons, such as the dopaminergic neurons that project from the substantia nigrapars compacta, (2) neuroinflammation with microglialactivation, and (3) abnormal deposition of specific proteins in the forms of Lewy bodies and Lewy neurites. (neuramedy.com)
  • Employing longer survival times (10 days after the nigral isotope injections) in order to enhance the ratio of "en passant" to terminal labeling produced a large increase in the occurrence of radiolabeled striatal axonal varicosities with the result that many symmetric synapses en passant were double-labeled with both the autoradiographic and the immunohistochemical markers. (nih.gov)
  • We recently demonstrated that TRPV1 activation by CAP increased the survival of nigral dopamine neurons by modulating the M1/M2 microglia/macrophage phenotype in lipopolysaccharide- (LPS-) injected SN [ 10 ], indicating that TRPV1 is a possible therapeutic target to treat PD. (hindawi.com)
  • The NTs then diffuse across the gap and "plug in" to receptors on the receiving neuron. (antiaging-nutrition.com)
  • When enough receptors are simultaneously activated by NTs, the neuron will either "fire" an electric current all over its surface membrane, if the transmitter/receptors are excitatory, or else the neuron will be inhibited from electrically discharging, if the NT/receptors are inhibitory. (antiaging-nutrition.com)
  • It does not appear to act via the dopaminergic system, but rather, it is theorized to act via GABAb receptors . (medscape.com)
  • Metoclopramide at these doses induces stereotyped cage climbing behaviour by releasing DA from the mesolimbic dopaminergic neurons with resultant activation of the postsynaptic mesolimbic D 2 DA receptors by the released DA. (who.int)
  • Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. (bvsalud.org)
  • iPSCs can become, for example, glutamatergic neurons or dopaminergic neurons. (labiotech.eu)
  • Therefore, a better comprehension of the genetic networks controlled by developmental transcription factors in differentiated mDA neurons may advance our molecular understanding of neurodegeneration in PD and open new therapeutic options. (nature.com)
  • This effect of age and genetic variance on disease pathology has not been recapitulated in cellular models before, and suggests that direct conversion to [dopaminergic neurons] could be used for differential diagnostics, drug screening, and disease modeling of late-onset neurodegenerative diseases," the researchers wrote. (infinitenest.org)
  • Dopaminergic and neurotrophic genetic polymorphisms modulate the implicit gender-science stereotype. (cdc.gov)
  • In contrast, these age-related features were not observed in iPSCs-derived dopaminergic neurons. (infinitenest.org)
  • We found that dopaminergic neurons expressing the OAMB octopamine receptor [6] specifically convey the short-term reinforcing effects of sweet taste [4]. (uni-konstanz.de)
  • On exposure to midbrain cues (sonic hedgehog, fibroblast growth factor 8 and basic fibroblast growth factor), DPSCs showed upregulation of dopaminergic neuron-specific transcription factors Nuclear Receptor related protein 1 (Nurr1), Engrailed 1 (En1) and paired-like homeodomain transcription factor 3 (Pitx3) as revealed by real-time RT-PCR. (manipal.edu)
  • 2016. α2-Adrenergic Receptor and Isoflurane Modulation of Presynaptic Ca2+ Influx and Exocytosis in Hippocampal Neurons. . (cornell.edu)
  • A drug called "memantine" which blocks the main GLU-excitotoxicity site in neurons - the NMDA GLU receptor (more on this later) - has been used clinically in Germany with significant success in treating Alzheimer's disease since 1991. (antiaging-nutrition.com)
  • abstract = "Several neuropsychiatric conditions, such as addiction and schizophrenia, may arise in part from dysregulated activity of ventral tegmental area dopaminergic (THVTA) neurons, as well as from more global maladaptation in neurocircuit function. (elsevier.com)
  • A dopaminergic neuron of the PPL1 cluster that has sparse terminals in the gamma lobe slice 1 (Aso et al. (virtualflybrain.org)
  • Treatment with diapocynin also significantly improved locomotor activity, restored dopamine and its metabolites, and protected dopaminergic neurons and their nerve terminals in this pre-clinical model of PD. (springer.com)
  • Previous ultrastructural examinations of monoamine neuron axon terminals often failed to identify a pre- and postsynaptic coupling, leading to the concept of 'volume' transmission. (ulaval.ca)
  • The active zone protein bassoon was found to be enriched in dopaminergic terminals that are in proximity to a target cell. (ulaval.ca)
  • Dysregulation of developmental transcription factors is implicated in dopaminergic neurodegeneration, but the underlying molecular mechanisms remain largely unknown. (nature.com)
  • Here we aimed at characterizing the dopaminergic neurons in the central nervous system of the honey bee, an insect that serves as an established model for the study of learning and memory. (umn.edu)
  • however, their ability to differentiate to functional neurons of the central nervous system remains to be studied. (manipal.edu)
  • This protein, known as PLCγ1, is particularly important in connecting the nerves, so that both the corpus callosum, which connects the cerebral cortex's left and right hemispheres, and the dopaminergic nervous system to function properly. (unist.ac.kr)
  • VTA neurons: Morphofunctional alterations in acute opiates withdrawal (Enrico et al. (yale.edu)
  • Under abnormal conditions, alpha-synuclein aggregates are released from neuronsand can reach neighboring neurons, affecting their function and viability. (neuramedy.com)
  • TLR2 also mediates neuron-to-neuron propagation of alpha-synuclein. (neuramedy.com)
  • Finally, we found that the proteins neurexin-1α and neuroligin-1 play a critical role in the formation of synapses by dopamine (DA) neurons. (ulaval.ca)
  • The model captures several salient features of DA neurons under different pharmacological manipulations and exhibits depolarization block for sufficiently high current pulses applied to the soma. (yale.edu)
  • A dopaminergic (DA) neuron model with a morphologicaly realistic dendritic architecture. (yale.edu)
  • Trade-off between dendritic democracy and independence in neurons with intrinsic subthreshold membrane potential oscillatio. (ens.fr)
  • This model provides mechanistic insights and explanations into the origin of a variety of experimentally observed membrane potential firing patterns in dopaminergic neurons, including N-methyl-D-aspartate-induced bursting and its dendritic origin. (physiomeproject.org)
  • We generated mouse Pitx3gfp/+ iPSC-derived DA neurons that, after fluorescent activated cell sorting (FACS) allowed comprehensive comparison to mesodiencephalic dopaminergic (mdDA) neurons from Fac-sorted Pitx3gfp/+ ventral midbrains. (omicsdi.org)
  • Transgenes used by us are, for example, fluorescent sensor proteins that allow us to monitor the spatio-temporal activity of neurons, or light-sensitive proteins by which neuronal activity can be stimulated through illumination. (uni-goettingen.de)