Background The efficient derivation of mature (Hb9+) motor neurons from embryonic stem cells is a sought-after goal in the understanding, and potential treatment, of motor neuron diseases. Conditions that promote the robust generation of motor neuron progenitors from embryonic stem cells and that promote the survival of differentiated motor neurons ex vivo are likely, therefore, to be critical in future biological/therapeutic/screening approaches. Previous studies have shown that astrocytes have a protective effect on differentiated motor neurons (in vivo and ex vivo), but it remains unclear whether astrocytes also play a beneficial role in the support of motor neuron progenitors. Here we explore the effect of murine astrocyte-conditioned medium on monolayer cultures of mouse embryonic stem cell-derived motor neuron progenitors. Results Our data show that wild-type astrocyte-conditioned medium significantly increases the number of Olig2+/Hb9- progenitors, which subsequently differentiate into ...
Spinal motor neurons are specified to innervate different muscle targets through combinatorial programs of transcription factor expression. Whether transcriptional programs also establish finer aspects of motor neuron subtype identity, notably the prominent functional distinction between alpha and gamma motor neurons, remains unclear. In this study, we identify DNA binding proteins with complementary expression profiles in alpha and gamma motor neurons, providing evidence for molecular distinctions in these two motor neuron subtypes. The transcription factor Err3 is expressed at high levels in gamma but not alpha motor neurons, whereas the neuronal DNA binding protein NeuN marks alpha but not gamma motor neurons. Signals from muscle spindles are needed to support the differentiation of Err3on/NeuNoff presumptive gamma motor neurons, whereas direct proprioceptive sensory input to a motor neuron pool is apparently dispensable. Together, these findings provide evidence that transcriptional programs define
Cultured spinal motor neurons are a valuable tool to study basic mechanisms of development, axon growth and pathfinding, and, importantly, to analyze the pathomechanisms underlying motor neuron diseases. However, the application of this cell culture model is limited by the lack of efficient gene transfer techniques which are available for other neurons. To address this problem, we have established magnetofection as a novel method for the simple and efficient transfection of mouse embryonic motor neurons. This technique allows for the study of the effects of gene expression and silencing on the development and survival of motor neurons. We found that magnetofection, a novel transfection technology based on the delivery of DNA-coated magnetic nanobeads, can be used to transfect primary motor neurons. Therefore, in order to use this method as a new tool for studying the localization and transport of axonal proteins, we optimized conditions and determined parameters for efficient transfection rates of |45%
Objective To assess the relationship between Bayesian MUNE and histological motor neuron counts in wild-type mice and in an animal model of ALS. Methods We performed Bayesian MUNE paired with histological counts of motor neurons in the lumbar spinal cord of wild-type mice and transgenic SOD1G93A mice that show progressive weakness over time. We evaluated the number of acetylcholine endplates that were innervated by a presynaptic nerve. Results In wild-type mice, the motor unit number in the gastrocnemius muscle estimated by Bayesian MUNE was approximately half the number of motor neurons in the region of the spinal cord that contains the cell bodies of the motor neurons supplying the hindlimb crural flexor muscles. In SOD1G93A mice, motor neuron numbers declined over time. This was associated with motor endplate denervation at the end-stage of disease. Conclusion The number of motor neurons in the spinal cord of wild-type mice is proportional to the number of motor units estimated by Bayesian ...
Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo. Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4::GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which ~1,000 are enriched in unc-4::GFP neurons relative to the average nematode embryonic cell. The reliability of these data was
We present electrophysiological evidence for the presence of central output synapses on crayfish walking leg motor neurones. The effect of these central outputs is that a motor neurone can exert tonic graded control over other motor neurones without the requirement for spiking. Excitatory interactions among synergists and inhibitory interactions among antagonists are described. This central coupling among leg motor neurones profoundly affects their responses to afferent input from an identified stretch receptor, the thoracocoxal muscle receptor organ (TCMRO). Injecting current into a motor neurone can change the gain of TCMRO reflexes in other motor neurones. Some motor neurones are also capable of reversing the sign of TCMRO reflexes by inhibiting reflex firing of antagonists and facilitating reflex activity in synergists. The implications of these central interactions of motor neurones in motor control are discussed. ...
Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo.. ...
The zebrafish detour (dtr) mutation generates a novel neuronal phenotype. In dtr mutants, most cranial motor neurons, especially the branchiomotor, are missing. However, spinal motor neurons are generated normally. The loss of cranial motor neurons is not due to aberrant hindbrain patterning, failure of neurogenesis, increased cell death or absence of hh expression. Furthermore, activation of the Hh pathway, which normally induces branchiomotor neurons, fails to induce motor neurons in the dtr hindbrain. Despite this, not all Hh-mediated regulation of hindbrain development is abolished since the regulation of a neural gene by Hh is intact in the dtr hindbrain. Finally, dtr can function cell autonomously to induce branchiomotor neurons. These results suggest that detour encodes a component of the Hh signaling pathway that is essential for the induction of motor neurons in the hindbrain but not in the spinal cord and that dtr function is required for the induction of only a subset of Hh-mediated ...
TY - JOUR. T1 - Inhibition linearizes firing rate responses in human motor units. T2 - implications for the role of persistent inward currents. AU - Revill, Ann L.. AU - Fuglevand, Andrew J. PY - 2017/1/1. Y1 - 2017/1/1. N2 - Key points: Motor neurons are the output neurons of the central nervous system and are responsible for controlling muscle contraction. When initially activated during voluntary contraction, firing rates of motor neurons increase steeply but then level out at modest rates. Activation of an intrinsic source of excitatory current at recruitment onset may underlie the initial steep increase in firing rate in motor neurons. We attempted to disable this intrinsic excitatory current by artificially activating an inhibitory reflex. When motor neuron activity was recorded while the inhibitory reflex was engaged, firing rates no longer increased steeply, suggesting that the intrinsic excitatory current was probably responsible for the initial sharp rise in motor neuron firing rate. ...
TY - JOUR. T1 - Motoneuron model of self-sustained firing after spinal cord injury. AU - Kurian, Mini. AU - Crook, Sharon. AU - Jung, Ranu. PY - 2011/11. Y1 - 2011/11. N2 - Under many conditions spinal motoneurons produce plateau potentials, resulting in self-sustained firing and providing a mechanism for translating short-lasting synaptic inputs into long-lasting motor output. During the acute-stage of spinal cord injury (SCI), the endogenous ability to generate plateaus is lost; however, during the chronic-stage of SCI, plateau potentials reappear with prolonged self-sustained firing that has been implicated in the development of spasticity. In this work, we extend previous modeling studies to systematically investigate the mechanisms underlying the generation of plateau potentials in motoneurons, including the influences of specific ionic currents, the morphological characteristics of the soma and dendrite, and the interactions between persistent inward currents and synaptic input. In ...
Accurate motor neuron development in the fly requires that axons target the correct muscles along the PD axis of the leg. This axis has several levels of refinement. The first level is the global PD axis of the leg. We find that Lin A only generates motor neurons that target the two more distal leg segments, the tibia and the femur. In addition, Lin A is the only lineage that produces motor neurons that target the tibia. In contrast, the seven Lin B motor neurons target all leg segments except the tibia. Thus, there is a PD bias built into these lineages.. A second level of refinement within the PD axis is targeting the correct muscle in individual leg segments. Among the Lin A-derived motor neurons, we observe a PD bias within the tibia and within the femur that correlates with birth date: the first half of the motor neurons born from Lin A have a strong bias for targeting proximal positions in these segments, whereas the later-born half of the motor neurons target distal muscles in these ...
Human pluripotent stem cells (hPSCs) are being applied in regenerative medicine and for the in vitro modeling of human intractable disorders. In particular, neural cells derived from disease-specific human induced pluripotent stem cells (hiPSCs) established from patients with neurological disorders have been used as in vitro disease models to recapitulate in vivo pathogenesis because neural cells cannot be usually obtained from patients themselves. In this study, we established a rapid, efficient, and simple method for efficiently deriving motor neurons from hPSCs that is useful for pathophysiological analysis and the development of drugs to treat motor neuron diseases. Treatment with GSK3β inhibitors during the initial phase of differentiation in combination with dual SMAD inhibition was sufficient to induce PAX6 + and SOX1 + neural progenitors within 1 week, and subsequent treatment with retinoic acid (RA) and purmorphamine, which activates sonic
Aging is related to multiple changes in muscle physiology and function. Previous findings concerning the effects of aging on motor unit discharge rate (DR) and fluctuations in DR and force are somewhat contradictory. Eight YOUNG and nine OLD physically active males performed isometric ramp (RECR) and isotonic (ISO) plantar flexions at 10 and 20% of surface EMG at MVC. Motor unit (MU) action potentials were recorded with intramuscular fine-wire electrodes and decomposed with custom build software Daisy. DR was lower in OLD in RECR-10% (17.9%, p ...
TY - JOUR. T1 - Reappraisal of VAChT-Cre. T2 - Preference in slow motor neurons innervating type I or IIa muscle fibers. AU - Misawa, Hidemi. AU - Inomata, Daijiro. AU - Kikuchi, Miseri. AU - Maruyama, Sae. AU - Moriwaki, Yasuhiro. AU - Okuda, Takashi. AU - Nukina, Nobuyuki. AU - Yamanaka, Tomoyuki. PY - 2016. Y1 - 2016. N2 - VAChT-Cre.Fast and VAChT-Cre.Slow mice selectively express Cre recombinase in approximately one half of postnatal somatic motor neurons. The mouse lines have been used in various studies with selective genetic modifications in adult motor neurons. In the present study, we crossed VAChT-Cre lines with a reporter line, CAG-Syp/tdTomato, in which synaptophysin-tdTomato fusion proteins are efficiently sorted to axon terminals, making it possible to label both cell bodies and axon terminals of motor neurons. In the mice, Syp/tdTomato fluorescence preferentially co-localized with osteopontin, a recently discovered motor neuron marker for slow-twitch fatigue-resistant (S) and ...
Scientists working to develop new treatments for neurodegenerative diseases have been stymied by the inability to grow human motor neurons in the lab. Motor neurons drive muscle contractions, and their damage underlies devastating diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy, both of which ultimately lead to paralysis and early death.. In new research, scientists at Washington University School of Medicine in St. Louis have converted skin cells from healthy adults directly into motor neurons without going through a stem cell state.. The technique makes it possible to study motor neurons of the human central nervous system in the lab. Unlike commonly studied mouse motor neurons, human motor neurons growing in the lab would be a new tool since researchers cant take samples of these neurons from living people but can easily take skin samples.. Click here to read more.. ...
TY - JOUR. T1 - Prevention of spinal motor neuron death by IGF-1 associating with the signal transduction systems in SODG93A transgenic mice. AU - Narai, Hisashi. AU - Manabe, Yasuhiro. AU - Murakami, Tetsuro. AU - Nagai, Makiko. AU - Kamiya, Tatsushi. AU - Abe, Koji. PY - 2007/11/13. Y1 - 2007/11/13. N2 - Background and aims: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease that is characterized by selective loss of central and peripheral motor neurons. There are many hypotheses about the underlying cause of this disease: one theory is that motor neurons lack crucially needed trophic factors, resulting in neuronal degeneration, cell death, and atrophy of target muscles. The role of insulin-like growth factor-1 (IGF-1) in ALS and its mechanism of action are important from both pathogenic and therapeutic points of view. Methods: The present study investigated the changes of IGF-1R? and the key intracellular downstream protein insulin receptor substrate-1 ...
A team of scientists has uncovered details of the cellular mechanisms that control the direct programming of stem cells into motor neurons. The scientists analyzed changes that occur in the cells over the course of the reprogramming process. They discovered a dynamic, multi-step process in which multiple independent changes eventually converge to change the stem cells into motor neurons.. There is a lot of interest in generating motor neurons to study basic developmental processes, as well as human diseases like ALS and spinal muscular atrophy, said Shaun Mahony, assistant professor of biochemistry and molecular biology at Penn State and one of the lead authors of the paper. By detailing the mechanisms underlying the direct programing of motor neurons from stem cells, our study not only informs the study of motor neuron development and its associated diseases, but also informs our understanding of the direct programming process and may help with the development of techniques to generate other ...
TY - JOUR. T1 - Changes in corticospinal drive to spinal motoneurones following visuo-motor skill learning in humans. AU - Perez, Monica A.. AU - Lundbye-Jensen, Jesper. AU - Nielsen, Jens B.. PY - 2006/6/15. Y1 - 2006/6/15. N2 - We have previously demonstrated an increase in the excitability of the leg motor cortical area in relation to acquisition of a visuo-motor task in healthy humans. It remains unknown whether the interaction between corticospinal drive and spinal motoneurones is also modulated following motor skill learning. Here we investigated the effect of visuo-motor skill training involving the ankle muscles on the coupling between electroencephalographic (EEG) activity recorded from the motor cortex (Cz) and electromyographic (EMG) activity recorded from the left tibialis anterior (TA) muscle in 11 volunteers. Coupling in the time (cumulant density function) and frequency domains (coherence) between EEG-EMG and EMG-EMG activity were calculated during tonic isometric dorsiflexion ...
ALS damages motor neurons in the brain and spinal cord. Motor neurons are nerve cells that control muscle movement. Upper motor neurons send messages from the brain to the spinal cord, and lower motor neurons send messages from the spinal cord to the muscles. Motor neurons are an important part of the bodys neuromuscular system.. The neuromuscular system lets our bodies move and is made up of the brain, many nerves, and muscles. Things that we do every day - like breathing, walking, running, lifting stuff, and even reaching for a glass of water - are all controlled by the neuromuscular system.. Over time, ALS causes the motor neurons in the brain and spinal cord to shrink and disappear, so that the muscles no longer receive signals to move. So, the muscles get smaller and weaker. Gradually the body becomes paralyzed, which means that the muscles no longer work.. However, someone with ALS, even at an advanced stage, can still see, hear, smell, and feel touch. The nerves that carry feelings of ...
In amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is progressive degeneration of motoneurones, it has been suggested that an intrinsic hyperexcitability of motoneurones (i.e. an increase in their firing rates), contributes to excitotoxicity and to disease onset. Here we show that there is no such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1 around the time of the first muscle fibre denervations. We showed that the recruitment current, the voltage threshold for spiking and the frequency-intensity gain in the primary range are all unchanged in most spinal motoneurones, despite an increased input conductance. On its own, increased input conductance would decrease excitability, but the homeostasis for excitability is maintained due to an upregulation of a depolarizing current that is activated just below the spiking threshold. However, this homeostasis failed in a
Injury to α-MNs is the most common type of lower motor neuron lesion. Damage may be caused by trauma, ischemia, and infection, among others. In addition, certain diseases are associated with the selective loss of α-MNs. For example, poliomyelitis is caused by a virus that specifically targets and kills motor neurons in the ventral horn of the spinal cord. Amyotropic lateral sclerosis likewise is associated with the selective loss of motor neurons. Paralysis is one of the most pronounced effects of damage to α-MNs. Because α-MNs provide the only innervation to extrafusal muscle fibers, losing α-MNs effectively severs the connection between the brainstem and spinal cord and the muscles they innervate. Without this connection, voluntary and involuntary (reflex) muscle control is impossible. Voluntary muscle control is lost because α-MNs relay voluntary signals from upper motor neurons to muscle fibers. Loss of involuntary control results from interruption of reflex circuits such as the tonic ...
Im sorry, its hard to guess what youve studied. Proprioception: Where the hell are you!? So you have receptors in your muscles and tendons that tell your body where you are and prevent you from pulling your own limbs off. Your skeletal muscles are innervated by alpha motor neurons and gamma motor neurons. The alpha motor neurons innervate the motor units of skeletal muscle (one motor unit is an array of muscle fibers that contract together, producing force), which are not what were talking about. Inside skeletal muscle is a muscle spindle, which is muscle tissue wrapped in collagen and has a fusiform (cigar) shape. This muscle is different and doesnt produce force, its just there to keep the whole spindle taut as the muscle around it shortens (everyone likes a tight spindle, amirite?). The gamma motor neurons are co-activated with the alpha motor neurons, so that as your bicep flexes the spindles inside shorten and stay taut (otherwise, as the muscle shortened the spindle would get floppy ...
C-type lectin (CLEC) receptors are important for initiating and shaping immune responses; however, their role in inflammatory reactions in the central nervous system after traumatic injuries is not known. The antigen-presenting lectin-like receptor gene complex (Aplec) contains a few CLEC genes, which differ genetically among inbred rat strains. It was originally thought to be a region that regulates susceptibility to autoimmune arthritis, autoimmune neuroinflammation and infection. The inbred rat strains DA and PVG differ substantially in degree of spinal cord motor neuron death following ventral root avulsion (VRA), which is a reproducible model of localized nerve root injury. A large F2 (DAxPVG) intercross was bred and genotyped after which global expressional profiling was performed on spinal cords from F2 rats subjected to VRA. A congenic strain, Aplec, created by transferring a small PVG segment containing only seven genes, all C-type lectins, ontoDA background, was used for further experiments
TY - JOUR. T1 - Postcontraction discharge of motor neurons in spinal animals. AU - Hutton, Robert S.. AU - Suzuki, Shuji. PY - 1979. Y1 - 1979. N2 - Muscle contraction of short duration gives rise to prolonged enhanced activity in muscle spindle afferent fibers. This postcontraction sensory discharge is sufficient in intensity to frequency-modulate motor neurons demonstrated to be tightly coupled to stretch receptors of the activated muscle. To determine whether or not postcontraction activation of motor neurons is dependent on supraspinal pathways, further experiments were done on cats with low spinal (T12) lesions. Sixty-one motor neurons were isolated in ventral root filaments and categorized according to their stretch reflex response and discharge pattern. Units found to be facilitated by stretch were significantly increased (P , 0.01) in resting discharge following contraction. Phasic motor neurons responded with a short postcontractile burst lasting only a few seconds whereas tonically ...
We introduce a space-state model in which the discharge activity of motor neurons is modeled as inhomogeneous Poisson processes and propose a method to quantify an abstract latent trajectory that represents the common input received by motor neurons. The approach also approximates the variation in synaptic noise in the common input signal. The model is validated with four data sets: a simulation of 120 motor units, a pair of integrate-and-fire neurons with a Renshaw cell providing inhibitory feedback, the discharge activity of 10 integrate-and-fire neurons, and the discharge times of concurrently active motor units during an isometric voluntary contraction. The simulations revealed that a latent state-space model is able to quantify the trajectory and variability of the common input signal across all four conditions. When compared with the cumulative spike train method of characterizing common input, the state-space approach was more sensitive to the details of the common input current and was ...
We introduce a space-state model in which the discharge activity of motor neurons is modeled as inhomogeneous Poisson processes and propose a method to quantify an abstract latent trajectory that represents the common input received by motor neurons. The approach also approximates the variation in synaptic noise in the common input signal. The model is validated with four data sets: a simulation of 120 motor units, a pair of integrate-and-fire neurons with a Renshaw cell providing inhibitory feedback, the discharge activity of 10 integrate-and-fire neurons, and the discharge times of concurrently active motor units during an isometric voluntary contraction. The simulations revealed that a latent state-space model is able to quantify the trajectory and variability of the common input signal across all four conditions. When compared with the cumulative spike train method of characterizing common input, the state-space approach was more sensitive to the details of the common input current and was ...
About 50% of spinal motoneurons undergo programmed cell death (PCD) after target contact, but little is known about how this process is initiated. Embryonic motoneurons coexpress the death receptor Fas and its ligand FasL at the stage at which PCD is about to begin. In the absence of trophic factors, many motoneurons die in culture within 2 d. Most (75%) of these were saved by Fas-Fc receptor body, which blocks interactions between Fas and FasL, or by the caspase-8 inhibitor tetrapeptide IETD. Therefore, activation of Fas by endogenous FasL underlies cell death induced by trophic deprivation. In the presence of neurotrophic factors, exogenous Fas activators such as soluble FasL or anti-Fas antibodies triggered PCD of 40-50% of purified motoneurons over the following 3-5 d; this treatment led to activation of caspase-3, and was blocked by IETD. Sensitivity to Fas activation is regulated: motoneurons cultured for 3 d with neurotrophic factors became completely resistant. Levels of Fas expressed by
Because microglial cells, the resident macrophages of the CNS, react to any lesion of the nervous system, they have for long been regarded as potential players in the pathogenesis of several neurodegenerative disorders including amyotrophic lateral sclerosis, the most common motor neuron disease in the adult. In recent years, this microglial reaction to motor neuron injury, in particular, and the innate immune response, in general, has been implicated in the progression of the disease, in mouse models of ALS. The mechanisms by which microglial cells influence motor neuron death in ALS are still largely unknown. Microglial activation increases over the course of the disease and is associated with an alteration in the production of toxic factors and also neurotrophic factors. Adding to the microglial/macrophage response to motor neuron degeneration, the adaptive immune system can likewise influence the disease process. Exploring these motor neuron-immune interactions could lead to a better understanding
The differentiation of floor plate cells and motor neurons can be induced by Sonic hedgehog (SHH), a secreted signaling protein that undergoes autoproteolytic cleavage to generate amino- and carboxy-terminal products. We have found that both floor plate cells and motor neurons are induced by the ami …
Abstract: Abdominal ganglia of crayfish contain identifiable neuropils, commissures, longitudinal tracts, and vertical tracts. To determine the functional significance of this ganglionic framework, we backfilled the following types of neurons with cobalt chloride: sensory hair afferents, slow and fast extensor motor neurons, the segmental stretch receptor neurons, and their inhibitory accessory cells. After the cobalt ions were precipitated and intensified, we studied the central projections of the filled neurons within the ganglionic structures. All of the axons of these neurons exit or enter each of the first five abdominal ganglia through the second pair of nerves. Our description of the central projections of the hair afferents is the first in the literature. These afferents innervate the large ventral horseshoe neuropil (HN) in the core of each ganglion. This neuropil is homologous to the insect ventral association centers, which also process sensory information. Furthermore, we discovered ...
Alibaba.com offers 314 muscle motors products. About 9% of these are gym equipment, 3% are ac motor, and 1% are dc motor. A wide variety of muscle motors options are available to you, such as totally enclosed, waterproof.
Two signals - an external one from retinoic acid and an internal one from the transcription factor Neurogenin2 - cooperate to activate chromatin (the basic material of chromosomes) and help determine that certain nerve progenitor cells become motor neurons, said researchers from Baylor College of Medicine in a report in the current issue of the journal Neuron.
As you have learned, every skeletal muscle fibre must be innervated by the axon terminal of a motor neuron in order to contract. Each muscle fibre is innervated by only one motor neuron. The actual group of muscle fibres in a muscle innervated by a single motor neuron is called a motor unit. The size of a motor unit is variable depending on the nature of the muscle.. A small motor unit is an arrangement where a single motor neuron supplies a small number of muscle fibres in a muscle. Small motor units permit very fine motor control of the muscle. The best example in humans is the small motor units of the extraocular eye muscles that move the eyeballs. There are thousands of muscle fibres in each muscle, but every six or so fibres are supplied by a single motor neuron, as the axons branch to form synaptic connections at their individual NMJs. This allows for exquisite control of eye movements so that both eyes can quickly focus on the same object. Small motor units are also involved in the many ...
This new study by the lab of Jeffrey Macklis assesses if, beside the well-established degeneration of (lower) spinal cord motor neurons in the widely used mutant SOD1/G93A mouse line, there is also a loss of (upper) corticospinal motor neurons (CSMNs), as is the case in actual human ALS. This is an important question and essential in order to judge the accuracy of this mouse ALS model.. Already in 2002, a study published in Neuroscience Letters by the lab of Surindar Cheema in Australia attempted to answer this question (Zang and Cheema, 2002). Both studies injected retrograde fluorogold labeling (at cervical levels) at different disease stages into high-expressing G93A mice (that reach endstage at 120 days) in order to mark the CSMNs and to assess their loss. The former study assessed loss at 60, 90, and 110 days of age (with negative littermates as controls), while the Macklis study did a more extensive approach starting at 30 days of age (then 60, 90, and 120 days) and comparing to wild-type ...
The spinal nucleus of the bulbocavernosus (SNB) contains 3-4 times more motoneurons in adult male rats compared to females. This large dimorphism in motoneuron number is produced perinatally by an androgen- regulated cell death. To determine if the early projections of the SNB to its target musculature may be involved in the creation of this sexual dimorphism, and how these projections might interact with androgens, HRP tracing techniques were used to retrogradely label SNB motoneurons during prenatal and postnatal development in males, females, and masculinized females. HRP labeling revealed that the prenatal formation of early projections of the SNB in males and females is comparable. SNB motoneuron number increases through the day before birth in all groups, and during this increase, labeled cells can be seen outside the SNB, which we hypothesize are in the process of migrating into the SNB from the lateral motoneuron column. Postnatally, SNB motoneuron number declines, especially in females, ...
The cellular diversity of the vertebrate central nervous system (CNS) relies upon the generation of distinct neuronal subclasses at defined positions and times from a relatively small pool of proliferating progenitors. As neural progenitors proliferate, they are exposed to secreted inductive signals that initiate cell fate decisions by regulating expression of transcription factors. These transcription factors, in turn, impose developmental restrictions on multipotent progenitor cells before ultimately effecting their final differentiation [1-3]. Understanding how extracellular and cell-intrinsic mechanisms are coordinated during CNS development is important not only for understanding embryonic patterning but also for gaining insight into the developmental potential of neuronal stem cells and progenitors isolated from different regions of the CNS [4].. Neural progenitors from different CNS regions exhibit varying degrees of restriction during their development. Heterochronic transplantation ...
MDGA proteins have been studied in humans (De Juan et al., 2002; Díaz-López et al., 2005), rats (Litwack et al., 2004), mice (Takeuchi et al., 2007), chickens (Fujimura et al., 2006) and medaka (Sano et al., 2009). Here we identified and cloned three MDGA orthologs in zebrafish, MDGA1, MDGA2A and MDGA2B. We found MDGA2A to be expressed in a subset of motoneurons, especially in the ones of the cranial, trigeminal and facial nerves. Morpholino mediated knockdown of MDGA2A led to aberrant cell migration of trigeminal neurons and to defasciculation and increased branch formation of the trigeminal as well as facial nerve. These results demonstrate that MDGA2A interactions are necessary for proper migration, axon outgrowth and bundling in cranial motoneurons.. In agreement with our current findings, MDGAs in other species have already been implicated in neuronal migration and axon guidance. In rats, MDGA positive cells were found in the pontine migratory stream, suggesting that these ...
Background: Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders. Effective therapeutic strategies are an unmet need for these disorders. Polyphenols, such as quercetin and resveratrol, are plant-derived compounds that activate sirtuins (SIRTs) and have shown promising results in some models of neuronal death, although their effects have been scarcely tested in models of motor neuron degeneration. Methods: In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the rat spinal cord tissue ...
Columbias Motor Neuron Center will transform our understanding of human health. For the first time, brilliant scientific minds are working together in a common approach to currently incurable motor neuron diseases: spinal muscular atrophy (SMA) in children and amyotrophic lateral sclerosis (ALS; Lou Gehrigs disease) in adults. New discoveries in the field of motor neuron biology will fuel the search for effective therapy for patients.. OUR MEMBERS. ...
A new way to artificially control muscles using light, with the potential to restore function to muscles paralyzed by conditions such as motor neuron disease and spinal cord injury, has been developed by scientists at UCL and Kings College London.. The technique involves transplanting specially-designed motor neurons created from stem cells into injured nerve branches. These motor neurons are designed to react to pulses of blue light, allowing scientists to fine-tune muscle control by adjusting the intensity, duration and frequency of the light pulses.. In the study, published this week in Science, the team demonstrated the method in mice in which the nerves that supply muscles in the hind legs were injured. They showed that the transplanted stem cell-derived motor neurons grew along the injured nerves to connect successfully with the paralyzed muscles, which could then be controlled by pulses of blue light.. Following the new procedure, we saw previously paralyzed leg muscles start to ...
The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity. The amounts of NT-4 messenger RNA present decreased after blockade of neuromuscular transmission with alpha-bungarotoxin and increased during postnatal development and after electrical stimulation in a dose-dependent manner. NT-4 immunoreactivity was detected in slow, type I muscle fibers. Intramuscular administration of NT-4 induced sprouting of intact adult motor nerves. Thus, muscle-derived NT-4 acted as an activity-dependent neurotrophic signal for growth and remodeling of adult motor neuron innervation. NT-4 may thus be partly responsible for the effects of exercise and electrical stimulation on neuromuscular performance.
Annotation: while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injuryImported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href=/manual/evidences#ECO:0000313>More…,/a>,/p> Automatic assertion inferred from database entriesi. ...
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The purpose of this study was to examine the effect of motor-unit recruitment on force variability by using computer simulated isometric contractions of a hand muscle (i.e., first dorsal interosseus). The force was simulated at 10 levels of excitation, ranging from 10 to 100% of maximum. Two recruitment conditions were simulated to compare the relative effect of motor-unit recruitment (MUR) on the relationship of force variability and level of force. One condition (40%MUR) recruited all motor units at 40% of the maximum excitation level, and the other (50%MUR) recruited all motor units at 50% of the maximum. The 40%MUR condition had a greater number of motor units than the 50%MUR group before the excitation level reached 50% of the maximum. The results showed that force variability increased at a faster rate before the completion of motor-unit recruitment and, thereafter, increased at a slower rate. In addition, the 40%MUR group showed greater force variability than the 50%MUR group. These data ...
Motor neuron. Scanning electron micrograph (SEM) of section through a motor neuron (nerve cell, dark pink) from the spinal cord, showing its nucleus (brick red, centre) and nucleolus (orange, centre). Motor neurones relay impulses from the central nervous system to muscle fibres. Magnification: x2600 when printed 10 centimetres wide. - Stock Image C011/6682
Literature References: Analog of thyrotropin releasing hormone TRH, q.v., with pronounced CNS activity. Prepn: H. Sugano et al., EP 168042; eidem, US 4665056 (1986, 1987 both to Tanabe Seiyaku): M. Suzuki et al., J. Med. Chem. 33, 2130 (1990). Radioimmunoassay determn in plasma and urine: S. Morikawa et al., J. Pharm. Biomed. Anal. 16, 1267 (1998). CNS pharmacology: M. Yamamura et al., Jpn. J. Pharmacol. 53, 451 (1990). Effect on motor neuron survival: Y. Iwasaki et al., Neurol. Res. 19, 613 (1997). Review of pharmacology, toxicology, and clinical trials: K. Kinoshita et al., CNS Drug Rev. 4, 25-41 (1998 ...
In addition to pursuing a disease in a dish model, researchers are using animal and other models to push the field forward. Already, scientists have made discoveries by working with mouse-derived embryonic stem cells, for example. Looking at an inherited form of ALS that involves a mutation in a protein called SOD1, Maniatis, Eggan and colleagues found one reason motor neurons die in ALS: changes in glia, the supporting cells that surround all motor neurons. The team generated motor neurons and glia from embryonic stem cells with the SOD1 mutation, then isolated glial cells from the tissue culture and added them to a culture of typical (non-ALS) motor neurons, as well as to motor neurons with the SOD1 mutation. The SOD1 glia killed both types of motor neurons, although the effect was more pronounced on the SOD1 motor neurons. It seems, then, that the expression of SOD1 in mutated glial cells causes the glia to secrete a toxic factor that kills the motor neurons. The discovery has led to a hunt ...
The new team results from the fusion of 2 teams and our objective is to capitalize on the complementary expertise to investigate key pathophysiological processes that lead to motor neuron (MN) degeneration and neuromuscular disorders such as Amyotrophic Lateral Sclerosis (ALS) and Congenital Myasthenia Syndromes. Our team assembles a unique spectrum of expertise allowing us to investigate all the components of the motor units (inputs to MNs arising from spinal and supraspinal circuits, properties of motor neurons, neuromuscular junctions, and muscle fibers ...
Movement coordination between opposite body sides relies on neuronal circuits capable of controlling muscle contractions according to motor commands. Trunk and limb muscles engage in distinctly lateralized behaviors, yet how regulatory spinal circuitry differs is less clear. Here, we intersect virus technology and mouse genetics to unravel striking distribution differences of interneurons connected to functionally distinct motor neurons. We find that premotor interneurons conveying information to axial motor neurons reside in symmetrically balanced locations while mostly ipsilateral premotor interneurons synapse with limb-innervating motor neurons, especially those innervating more distal muscles. We show that observed distribution differences reflect specific premotor interneuron subpopulations defined by genetic and neurotransmitter identity. Synaptic input across the midline reaches axial motor neurons preferentially through commissural axon arborization, and to a lesser extent, through ...
In this video Im going to talk about upper motor neurons. So upper motor neurons, which are different than the motor neurons we talked about before, which are the lower motor neurons. Now when we talked about the lower motor neurons, we talked about how they have their somas, either in the brain stem or in the spinal cord, and how they send axons out through nerves in the peripheral nervous system to synapse on and control skeletal muscle cells to tell those skeletal muscle cells when to contract and we talked about that the lower motor neurons that pass through spinal nerves primarily control muscles of the limbs and the trunk, and lower motor neurons that pass through cranial nerves primarily control the skeletal muscles of the head and the neck. But now were going to talk about the upper motor neurons, because it turns out that while the lower motor neurons are controlling the skeletal muscle cells and telling them when to contract, upper motor neurons are the ones that are controlling the ...
TY - JOUR. T1 - Tracking motor unit action potentials in the tibialis anterior during fatigue. AU - Beck, R.B.. AU - OMalley, M.J.. AU - Stegeman, D.F.. AU - Houtman, C.J.. AU - Connolly, S.. AU - Zwarts, M.J.. PY - 2005. Y1 - 2005. N2 - New surface electromyogram (SEMG) techniques offer the potential to advance knowledge of healthy and diseased motor units. Conduction velocity (CV) estimates, obtained from indwelling electrodes, may provide diagnostic information, but the standard method of CV estimation from SEMG may be of only limited value. We developed a motor unit (MU) tracking algorithm to extract motor unit conduction velocity (MUCV) and motor unit action potential (MUAP) amplitude estimates from SEMG. The technique is designed to provide a noninvasive means of accessing fatigue and recruitment behavior of individual MUs. We have applied this MU tracking algorithm to SEMG data recorded during isometric fatiguing contractions of the tibialis anterior (TA) muscle in nine healthy subjects, ...
One physiological method for estimating the motor unit number in a muscle depends on dividing into the maximum compound muscle action potential, the potential average of the first few motor unit potentials excited by a motor nerve stimulus above motor threshold. To be valid, such an average unit potential size must be representative of the whole motor unit population. This assumption may not be justified. The present study has shown that there are single motor units in healthy and abnormal, thenar, and EDB motor unit populations, many times larger than any motor unit excited close to the motor threshold. This finding suggests that previously reported motor unit estimates may not only be an overestimate of the true motor unit population number, but have excluded much larger motor units with higher thresholds. Low motor unit estimates in neuropathies may result from a change in the order of activation of motor units with the appearance of larger motor units, normally of higher threshold among the ...
Abstract: The purpose of the current investigation was to assess the effect of an acute bout of whole body vibration (WBV) exercise on muscle force output and motor neuron excitability. Nineteen recreationally trained college-aged males were randomly assigned to a WBV (n = 10) or a sham (S, n = 9) group. The WBV group completed a series of static, body weight squats on a vibrating platform at 30 Hz and an amplitude of ~3.5 mm (vertical), whereas the S group performed the same series of exercises but without vibration. Measurements were performed before (Pre) and then immediately post-exercise (Imm Post), 8 minutes post-exercise (8-Min Post), or 16 minutes post-exercise (16-Min Post) during 3 different testing sessions. The measurements involved a ballistic isometric maximum voluntary contraction (MVC) of the triceps surae muscle complex and electrical stimulation of the tibial nerve for assessment of motor neuron excitability by analyzing H-reflex and M-wave responses (Hmax/Mmax ratio). ...
Objective To use our Bayesian method of motor unit number estimation (MUNE) to evaluate lower motor neuron degeneration in ALS. Methods In subjects with ALS we performed serial MUNE studies. We examined the repeatability of the test and then determined whether the loss of MUs was fitted by an exponential or Weibull distribution. Results The decline in motor unit (MU) numbers was well-fitted by an exponential decay curve. We calculated the half life of MUs in the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and/or extensor digitorum brevis (EDB) muscles. The mean half life of the MUs of ADM muscle was greater than those of the APB or EDB muscles. The half-life of MUs was less in the ADM muscle of subjects with upper limb than in those with lower limb onset. Conclusions The rate of loss of lower motor neurons in ALS is exponential, the motor units of the APB decay more quickly than those of the ADM muscle and the rate of loss of motor units is greater at the site of onset of ...
We performed proton magnetic resonance spectroscopic imaging (1H-MRSI) in patients with motor neuron disease (MND) to evaluate the distribution and extent of cortical neuron damage or loss as reflected by decreased N-acetyl (NA) to creatine (Cr) resonance intensity ratios. We examined premotor (superior frontal gyrus), primary motor (precentral gyrus), primary sensory (postcentral gyrus), and parietal (superior parietal gyrus/precuneus) neocortical regions of 12 patients with MND and six normal control subjects. Patients with MND were representative of three syndromes: amyotrophic lateral sclerosis (ALS) with definite lower motor neuron and upper motor neuron signs, MND with probable upper motor neuron signs (PUMNS), and progressive spinal muscular atrophy (PSMA) with lower motor neuron signs only. Compared with healthy controls, ALS patients had a significant decrease in NA/Cr resonance intensity ratios, most prominently in the primary motor cortex (p , 0.001) but also, to varying degrees, in ...
What is motor neurone disease?. Motor neurone disease describes a group of diseases that affect the nerves (motor neurones) in the brain and spinal cord responsible for voluntary movement and muscle control. With motor neurone disease, messages from these nerves gradually stop reaching the muscles, leading them to weaken and waste1 (atrophy). It is a rapidly progressive, invariably fatal, neurological disease that can significantly shorten life expectancy, but some people live with it for many years. There is no known cure but there are interventions, such as therapies, equipment and medications, that can reduce the impact the disease has on daily life2 and ultimately achieve the best possible quality of life for individuals.. What is amyotrophic lateral sclerosis?. An individual may be diagnosed with a particular type of motor neurone disease. Each type is a way of describing how the disease is likely to affect an individual and does not describe a completely separate disease, just a different ...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1(+/+) stem cell line do not display the hyperexcitability phenotype. SOD1(A4V/+) ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons, a deficit that may underlie their hyperexcitability. The Kv7 channel activator retigabine both blocks the hyperexcitability and improves motor neuron survival in vitro when tested in SOD1 mutant ALS cases. Therefore, electrophysiological characterization of human stem cell-derived neurons ...
Scientists working to develop new treatments for neurodegenerative diseases have been stymied by the inability to grow human motor neurons in the lab. Motor neurons drive muscle contractions, and their damage underlies devastating diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy, both of which ultimately lead to paralysis and early death.. In new research, scientists at Washington University School of Medicine in St. Louis have converted skin cells from healthy adults directly into motor neurons without going through a stem cell state.. The technique makes it possible to study motor neurons of the human central nervous system in the lab. Unlike commonly studied mouse motor neurons, human motor neurons growing in the lab would be a new tool since researchers cant take samples of these neurons from living people but can easily take skin samples.. The study is published Sept. 7 in the journal Cell Stem Cell.. Avoiding the stem cell phase eliminates ethical concerns raised ...
Symptoms may or may not be noticed until much later in life even in the late 50s throughout the 70s. The disease can easily progress very fast to making the individuals unable to do things for themselves. Symptoms can also vary from person to person and be much more severe in some instances for those who have a worse off condition. Symptoms usually progressively get worse over time and will eventually become difficult to live with when the damages it produces to the neurons makes it nearly impossible to do anything. The common symptoms that are usually noticed by those who are affected include:. Weakness - Weakness is one of the major problems that is experienced because they are unable to forcibly do something with their muscles even though their muscles are fine at first. The weakness can be very slight and can grow with time to not being able to move the muscles at all. This can lead to even more severe problems with time.. Muscle Atrophy - Muscle atrophy occurs from several reasons but it ...
Abstract. The recent investigation suggested that the TDP-43 protein was closely related to the motor neuron degeneration in amyotrophic lateral sclerosis (ALS), but the pathogenesis contributed to motor neuron degeneration largely remained unknown. Therefore, we detected the alteration of TDP-43 expression and distribution in the adult spinal cord of the SOD1 G93A transgenic mouse model for searching the possible pathogenesis of ALS. We examined the TDP-43 expression and distribution in the different anatomic regions, segments and neural cells in the adult spinal cord at the different stages of the SOD1 wild-type and G93A transgenic model by the fluorescent immunohistochemical technology. We revealed that the amount of TDP-43 positive cell was cervical,lumbar,thoracic segment, that in the ventral horn was more than that in the dorsal horn, a few of TDP-43 protein sparsely expressed and distributed in the other regions, the TDP-43 protein werent detected in the white matter and the central ...
Upper motor neurons and lower motor neurons act to carry nerve impulses from the brain out to the muscles in the body.Upper motor neurons supply input to the lower motor neurons. They do this by either synapsing directly to lower motor neurons, or by s...
Motor neuron differentiation is accompanied by the expression of a LIM homeodomain transcription factor, Islet1 (ISL1). To assess the involvement of ISL1 in the generation of motor neurons, we analyzed cell differentiation in the neural tube of embryos in which ISL1 expression has been eliminated by …
Motor neuron disease (MND), also commonly known as amyotrophic lateral sclerosis (ALS), is a chronic neurodegenerative disorder of the motor system in adults, characterized by the loss of motor neurons in the cortex, brain stem and spinal cord. This book presents current research from across the globe in the study of the causes, classification and treatments of MND, including membrane trafficking defects as determinants of motor neuron susceptibility and degeneration in ALS; motorneurons specific calcium dysregulation and perturbed cellular calcium homeostasis in ALS; stem cells and their application in ALS treatment; excitotoxicity and selective motor neuron degeneration and therapeutic intervention and assistive technology treatments. (Imprint: Nova Biomedical ). ...
The central nervous system is responsible for the orderly recruitment of motor neurons, beginning with the smallest motor units.[3] Hennemans size principle indicates that motor units are recruited from smallest to largest based on the size of the load. For smaller loads requiring less force, slow twitch, low-force, fatigue-resistant muscle fibers are activated prior to the recruitment of the fast twitch, high-force, less fatigue-resistant muscle fibers. Larger motor units are typically composed of faster muscle fibers that generate higher forces.[4] The central nervous system has two distinct ways of controlling the force produced by a muscle through motor unit recruitment: spatial recruitment and temporal recruitment. Spatial recruitment is the activation of more motor units to produce a greater force. Larger motor units contract along with small motor units until all muscle fibers in a single muscle are activated, thus producing the maximum muscle force. Temporal motor unit recruitment, or ...
Motor neuron disease is clinically characterized by progressive muscle wasting leading to total muscle paralysis. A long history of pathological study of patients has firmly established that the primary lesion site is in spinal and cortical motor neurons. In addition to the wide-spread loss of these neurons, neuronal abnormalities including massive accumulation of neurofilaments in cell bodies and proximal axons have been also widely observed, particularly in the early stages of the disease. To test whether high accumulation of neurofilaments directly contributes to the pathogenic process, transgenic mice that produce high levels of neurofilaments in motor neurons have been generated. These transgenic mice show most of the hallmarks observed in motor neuron disease, including swollen perikarya with eccentrically localized nuclei, proximal axonal swellings, axonal degeneration and severe skeletal muscle atrophy. These data indicate that extensive accumulation of neurofilaments in motor neurons ...
A new toxic entity associated with genetically inherited forms of dementia and motor neuron disease has been identified by scientists at the UCL Institute of Neurology. The toxin is the result of a genetic mutation that leads to the production of RNA molecules which could be responsible for the diseases. The findings are published in the journal Acta Neuropathologica.. Frontotemporal dementia and motor neuron disease are related neurodegenerative diseases that affect approximately 15,000 people in the UK. Frontotemporal dementia causes profound personality and behaviour changes. Motor neuron disease leads to muscle weakness and eventual paralysis.. The most common known cause for both frontotemporal dementia and motor neuron disease is an unusual genetic mutation in the C9orf72 gene. The mutation involves a small string of DNA letters at the beginning of the gene, which expand massively to produce thousands of copies.. The new research, funded by Alzheimers Research UK and the Medical Research ...
Motor neurone disease is a neurodegenerative condition with a significant morbidity and shortened life expectancy. Hypoventilatory respiratory failure is the most common cause of death and respiratory function significantly predicts both survival and quality of life in patients with motor neurone disease. Accordingly, supporting and maintaining respiratory function is important in caring for these patients. The most significant advance in motor neurone disease care of recent years has been the domiciliary provision of non-invasive ventilation for treating respiratory failure. Neuromuscular respiratory weakness also leads to ineffective cough and retained airways secretions, predisposing to recurrent chest infections. In this review, we discuss current practice and recent developments in the respiratory management of motor neurone disease, in terms of ventilatory support and cough augmentation.. ...
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My first encounter with Motor Neurone Disease was about twenty five years ago. My Uncle Basil was a big man, hed worked down the pit most of his life and had the build to show for it (the phrase youre looking for is built like a brick sh*thouse). As a kid I always thought he was a giant, and even as I grew up he was still a big man. Then he developed Motor Neurone Disease.. The rate at which he lost weight was frightening and he went downhill really quickly. It wasnt long before we lost him and the speed and aggression of Motor Neurone Disease is something Ive never forgotten so when a friend told me she was running a marathon to raise funds for MNDA (the Motor Neurone Disease Association) and needed some publicity photographs I jumped at the chance to help ...
Hypotonia can be due to damage to alpha neurons or Ia afferents carrying sensory information to the alpha neurons. This creates a decrease in muscle tone. Opposite to this, hypertonia is caused by damage to descending pathways that terminate in the spinal cord. It increases muscle tone by increasing the total responsiveness of alpha motor neurons from its Ia sensory input.. Spasms can be caused by a disparity between how much alpha and gamma motor neurons are firing, i.e. too much gain of one or the other. The imbalance causes an inaccurate reading from muscle receptors in the muscle spindle. Therefore, the sensory neurons feeding back to the brain and spinal cord are misleading. For example, if a patient has over active gamma motor neurons, there will be a resistance to passive movement causing stiffness, also called spasticity. This is often found in individuals with damage to higher centers affecting the descending pathways. This can sometimes cause a gamma-bias (constant discharge of some ...
Motor Neuron Diseases (MND) are a group of progressive neurological disorders that destroy cells that control essential muscle activity such as breathing, walking, speaking, and swallowing. Basically, Messages from nerve cells in the brain (called upper motor neurons) are transmitted to nerve cells in the brain stem and spinal cord (called lower motor neurons), and from them to particular muscles. When there are impediments in these signals, the result can be gradual muscle weakening, wasting away, and uncontrollable twitching (called fasciculations).
It was important to us to do a blog on the current state of Stem Cell Research. We have witnessed the disappointment of many in the community based on the current Clinical Hold that has been put on the SMA clinical trial. It is important to point out The Sophias Cure Foundation has supported and will continue to support Stem Cell Research. We believe Motor Neuron Research is part of the big picture in regards to Spinal Muscular Atrophy. Eventually Motor Neurons will have to be replaced to correct the loss of Motor Neurons in our children. I think it is important for the community to understand the recent correction that has taken place in regards to this field of research. Currently there are some major hurdles that must be overcome before Stem Cells can replace Motor Neurons that have been lost. What is a possibility for Stem cells is to offer Neurotrophic Support. This suggests that Stem Cells could possibly help existing motor neurons, but it is not replacing motor neurons that have been ...
Amyotrophic Lateral Sclerosis is a progressively lethal motor neuron disease with no known cure. Genetic evidence suggests a diverse set of underlying causes with broad links to protein quality control and DNA/RNA homeostasis. Cellular evidence suggests that ALS is not only caused by defects within motor neurons but also through significant contributions from non-neuronal cells. In particular, astrocytes have been proposed to gain properties that greatly accelerate disease progression. The most common ALS-causative genes are widely expressed throughout the nervous system, including in astrocytes. While many studies have focused on cell-autonomous defects in ALS motor neurons, less is known about mechanisms by which non-neuronal cells such as astrocytes contribute to motor neuron degeneration. The studies presented here explore the behavior of astrocytes in models of ALS caused by mutations in the DNA/RNA binding protein Fused in Sarcoma (FUS). Here, we studied whether over-expression of wild-type FUS or
Looking for online definition of final motor neuron in the Medical Dictionary? final motor neuron explanation free. What is final motor neuron? Meaning of final motor neuron medical term. What does final motor neuron mean?
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder involving the degeneration of motor neurons accompanied by skeletal muscle atrophy and paralysis. Transgenic mice ubiquitously overexpressing human SOD1 mutants develop motor neuron disease resembling ALS (Gurney et al., 1994) and provide useful model to test potential therapeutic strategies in disease treatment.. Notably, restriction of SOD1 mutant expression selectively to post-natal motor neurons failed to produce detectable sign of pathology or motor-neuron disease (Lino et al., 2002), suggesting that other cell types may be involved in ALS-associated neurodegeneration.. Indeed, analysis of chimeras generated between wild-type and SOD1 mutant mouse embryonic cells revealed that wild-type non neuronal cells in adult chimeric animals extended the survival of SOD1 mutant motor neurons, suggesting that the neurodegenerative action of mutant SOD1 may operate through a dominant paracrine activity emanating from nonneuronal cells ...
TY - JOUR. T1 - Ventral root avulsion. T2 - An experimental model of death of adult motor neurons. AU - Koliatsos, Vassilis E.. AU - Price, William L.. AU - Pardo, Carlos A.. AU - Price, Donald L.. PY - 1994/4/1. Y1 - 1994/4/1. N2 - The present study proposes a reproducible model of experimental degeneration of adult motor neurons in the rat. Avulsion of ventral roots in the adult lumbar cord transects motor axons at the root exit and leads to retrograde cell death of 80% of motor neurons 2 weeks later; this result follows a series of retrograde changes, including chromatolysis, loss of transmitter phenotype, and accumulation of phosphorylated neurofilaments in perikarya. Glial cells recruited at the site of retrograde injury express both microglia‐specific epitopes (as exemplified by OX‐42 immunoreactivity) and macrophage‐specific markers (e.g., ED‐1 immunoreactivity). Macrophage‐specific markers become particularly intense 7 days postaxotomy and provide additional evidence of active ...
TY - JOUR. T1 - Motor unit composition has little effect on the short-range stiffness of feline medial gastrocnemius muscle. AU - Cui, Lei. AU - Perreault, Eric J.. AU - Sandercock, Thomas G.. PY - 2007/9. Y1 - 2007/9. N2 - Studies on skinned fibers and single motor units have indicated that slow-twitch fibers are stiffer than fast-twitch fibers. This suggests that skeletal muscles with different motor unit compositions may have different short-range stiffness (SRS) properties. Furthermore, the natural recruitment of slow before fast motor units may result in an SRS-force profile that is different from electrical stimulation. However, muscle architecture and the mechanical properties of surrounding tissues also contribute to the net SRS of a muscle, and it remains unclear how these structural features each contribute to the SRS of a muscle. In this study, the SRS-force characteristics of cat medial gastrocnemius muscle were measured during natural activation using the crossed-extension reflex, ...
Brain in motor neurone disease. FLAIR magnetic resonance imaging (MRI) scan of a coronal section through the brain of a 32-old patient with motor neurone disease, showing hyperintensity of the pyramidal tracts. Motor neurone disease (also Charcot disease or amyotrophic lateral sclerosis), is a degenerative neurological disorder that involves the death of neurons (nerve cells). - Stock Image C023/9798
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition that primarily affects the motor system and shares many features with frontotemporal dementia (FTD). Evidence suggests that ALS is a dying-back disease, with peripheral denervation and axonal degeneration occurring before loss of motor neuron cell bodies. Distal to a nerve injury, a similar pattern of axonal degeneration can be seen, which is mediated by an active axon destruction mechanism called Wallerian degeneration. Sterile alpha and TIR motif-containing 1 (Sarm1) is a key gene in the Wallerian pathway and its deletion provides long-term protection against both Wallerian degeneration and Wallerian-like, non-injury induced axonopathy, a retrograde degenerative process that occurs in many neurodegenerative diseases where axonal transport is impaired. Here, we explored whether Sarm1 signalling could be a therapeutic target for ALS by deleting Sarm1 from a mouse model of ALS-FTD, a TDP-43Q331K, YFP-H double transgenic mouse.
TY - JOUR. T1 - Generation of spinal motor neurons from human fetal brain-derived neural stem cells. T2 - Role of basic fibroblast growth factor. AU - Jordan, Paivi M.. AU - Ojeda, Luis D.. AU - Thonhoff, Jason R.. AU - Gao, Junling. AU - Boehning, Darren. AU - Yu, Yongjia. AU - Wu, Ping. PY - 2009/2/1. Y1 - 2009/2/1. N2 - Neural stem cells (NSCs) have some specified properties but are generally uncommitted and so can change their fate after exposure to environmental cues. It is unclear to what extent this NSC plasticity can be modulated by extrinsic cues and what are the molecular mechanisms underlying neuronal fate determination. Basic fibroblast growth factor (bFGF) is a well-known mitogen for proliferating NSCs. However, its role in guiding stem cells for neuronal subtype specification is undefined. Here we report that in-vitro-expanded human fetal forebrain-derived NSCs can generate cholinergic neurons with spinal motor neuron properties when treated with bFGF within a specific time window. ...
Embryonic stem (ES) cells are a unique system to model mammalian embryonic development in an accessible in vitro setting. The ability of ES cells to generate any cell type found in our organism can be harnessed to study how cellular diversity is established during development. We demonstrate this by recapitulating key aspects of neural tube patterning and spinal cord development in differentiating ES cells, leading to efficient production of spinal motor neurons in vitro. Access to a virtually unlimited supply of spinal motor neurons creates a unique opportunity to decipher molecular processes governing the conversion of a pluripotent stem cell to a committed and differentiated cell type at global and comprehensive level. Currently we examine how differentiating cells integrate patterning signals and translate them into lasting changes in chromatin architecture and in patterns of gene expression. We believe that the studies will not only elucidate the complex, yet highly reproducible processes ...
The Ozdinler Lab generated a novel reporter line in which both the sensory and the motor neurons are genetically labeled with a fluorescent green protein, allowing visualization and precise cellular analyses for motor and sensory systems simultaneously. The lab previously published this characterization of motor neuron component in the Journal of Neuroscience and is now reporting the sensory component in PLOS One. This recent publication is a collaborative work with Drs. Richard Miller and Amy Paller.. Dr. Ozdinler is organizing a Symposium at the Society for Neuroscience (SFN) about the importance of upper motor neurons for motor neuron diseases. This will be the first symposium about upper motor neurons at SFN.. The Ozdinler Lab will be presenting four abstracts at the American Neurological Association meeting, one abstract at the International Brain Research Organization meeting, six abstracts at Society for Neuroscience and two abstracts at the ALS/MND meeting this year. These abstracts ...
Upper motor neuron disease: Muscle weakness typical of upper motor neuron disease is seen in stroke, producing weakness of one side of the body. The arm is typically flexed, the leg is extended, and the limbs have increased tone. Some movement may be preserved, although…
Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro. Knockdown of Src or c-Abl with small interfering RNAs (siRNAs) also rescued ALS motor neuron degeneration. One of the hits, bosutinib, boosted autophagy, reduced the amount of misfolded mutant SOD1 protein, and attenuated altered expression of mitochondrial genes. Bosutinib also increased survival in vitro of ALS iPSC-derived motor neurons from patients with sporadic ALS or other forms of familial ALS caused by mutations in TAR DNA ...
The amount of documented increase in motor unit (MU) synchronization with fatigue and its possible relation with force tremor varies largely, possibly due to inhomogeneous muscle activation and methodological discrepancies and limitations. The aim of this study was to apply a novel surface electromyographical (EMG) descriptor for MU synchronization based on large MU populations to examine changes in MU synchronization with fatigue at different sites of a muscle and its relation to tremor. Twenty-four subjects performed an isometric elbow flexion at 25% of maximal voluntary contraction until exhaustion. Monopolar EMG signals were recorded using a grid of 130 electrodes above the biceps brachii. Changes in MU synchronization were estimated based on the sub-band skewness of EMG signals and tremor by the coefficient of variation in force. The synchronization descriptor was dependent on recording site and increased with fatigue together with tremor. There was a general association between these two ...
Motor neuron diseases are the most common neurological disorders found in the age ranges between 35-70years, which selectively affect the motor neurons. Amyotrophic lateral sclerosis (ALS) is a fatal motorneuron disease that assails the nerve cells in the brain. This disease progressively degenerates the motorcells in the brain and spinal cord, which are responsible for controlling the muscles that enable human tomove around, breathe, speak, and swallow. The electromyography (EMG) signals are the biomedicalsignals that are used to study the muscle function based on the electrical signal originated from themuscles. As the nervous system controls the muscle activity, the EMG signals can be viewed and analyzedin order to detect the indispensable features of the ALS disease in individuals. In this paper, analyzing thetime and frequency domain behaviour of the EMG signals obtained from several normal persons and theALS patients, some characteristic features, such as autocorrelation, zero crossing rate and
Motor Neuron Disease Motor neurone disease is a neurological condition that causes the progressive degeneration of specialised nerve cells, called motor neurons, in the brain and spinal cord. It has no known cause and is invariably fatal, with a likely life expectancy of 2 - 4 years from diagnosis. In New Zealand about 300 people … Continue reading. ...
TY - JOUR. T1 - Excitatory postsynaptic potentials evoked by ventral root stimulation in neonate rat motoneurons in vitro. AU - Jiang, Z. G.. AU - Shen, E.. AU - Wang, M. Y.. AU - Dun, N. J.. PY - 1991/1/1. Y1 - 1991/1/1. N2 - Intracellular recordings were made from antidromically identified motoneurons in transverse (500 μm) lumbar spinal cord slices of neonatal (12-20 day) rats. Electrical stimulation of ventral rootlets evoked, with or without an antidromic spike or initial segment potential, a depolarizing response (latency, 1-4.2 ms), a hyperpolarizing response (latency, 1.5-3.5 ms), or a combination of two preceding responses in 38, 6, and 8% of motoneurons investigated. The hyperpolarizing response was reversibly eliminated by low Ca2+ (0.25 mM), d-tubocurarine (d-Tc; 10 μM) or strychnine (1 μM), suggesting that this response represents an inhibitory postsynaptic potential (IPSP) mediated by glycine or a related substance released from inhibitory interneurons subsequent to their ...
Motor neurone disease (MND) is a fatal, rapidly progressing neurological disease. It attacks the nerves that control movement (motor neurones) so that muscles no longer work.. Motor neurones control important muscle activity such as gripping, walking, speaking, swallowing and breathing. As these nerves are attacked, messages gradually stop reaching muscles. This initially leads to weakness and wasting and then, eventually, severe paralysis and breathing difficulties.. Mental abilities and senses are not usually affected and therefore patients generally remain aware of their deteriorating physical condition.. There is no cure for MND, it is always fatal, but some people live with it for many years. Professor Stephen Hawking lived with MND for more than 50 years, having been diagnosed at the age of just 21. Amyotrophic lateral sclerosis (ALS) is the most common type of MND and is the umbrella term used in the USA for all forms of the disease. ...
Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrigs disease or classical motor neuron disease, is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away, and twitch. Eventually the ability of the brain to start and control voluntary movement is lost.
TY - JOUR. T1 - Endoplasmic reticulum lipid rafts and upper motor neuron degeneration. AU - Belzil, Véronique V.. AU - Rouleau, Guy A.. PY - 2012/10/1. Y1 - 2012/10/1. UR - http://www.scopus.com/inward/record.url?scp=84868129518&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84868129518&partnerID=8YFLogxK. U2 - 10.1002/ana.23678. DO - 10.1002/ana.23678. M3 - Editorial. C2 - 23109142. AN - SCOPUS:84868129518. VL - 72. SP - 479. EP - 480. JO - Annals of Neurology. JF - Annals of Neurology. SN - 0364-5134. IS - 4. ER - ...