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Spinal Motor Neurons (spinal + motor_neuron)
Selected AbstractsDependence of axon initial segment formation on Na+ channel expressionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2005Xiaorong Xu Abstract Spinal motor neurons were isolated from embryonic rats, and grown in culture. By 2 days in vitro, the axon initial segment was characterized by colocalization and clustering of Na+ channels and ankyrinG. By 5 days, NrCAM, and neurofascin could also be detected at most initial segments. We sought to determine, as one important aim, whether Na+ channels themselves played an essential role in establishing this specialized axonal region. Small hairpin RNAs (shRNAs) were used to target multiple subtypes of Na+ channels for reduced expression by RNA interference. Transfection resulted in substantial knockdown of these channels within the cell body and also as clusters at initial segments. Furthermore, Na+ currents originating at the initial segment, and recorded under patch clamp, were strongly reduced by shRNA. Control shRNA against a nonmammalian protein was without effect. Most interestingly, targeting Na+ channels also blocked clustering of ankyrinG, NrCAM, and neurofascin at the initial segment, although these proteins were seen in the soma. Thus, both Na+ channels and ankyrinG are required for formation of this essential axonal domain. Knockdown of Na+ channels was somewhat less effective when introduced after the initial segments had formed. Disruption of actin polymerization by cytochalasin D resulted in multiple initial segments, each with clusters of both Na+ channels and ankyrinG. The results indicate that initial segment formation occurs as Na+ channels are transported into the nascent axon membrane, diffuse distally, and link to the cytoskeleton by ankyrinG. Subsequently, other components are added, and stability is increased. A computational model closely reproduced the experimental results. © 2005 Wiley-Liss, Inc. [source] Potential roles of Alzheimer precursor protein A4 and ,-amyloid in survival and function of aged spinal motor neurons after axonal injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Yuanyun Xie Abstract To study the potential role of Alzheimer precursor protein A4 (APP) and ,-amyloid (A/,) on aging motor neuron survival, expression of APP, A/,, and choline acetyltransferase (ChaT) were investigated in aged rats after either distal axotomy or root avulsion injury. Approximately 45% in number of total aged spinal motor neuron were normally APP-positive. A/,-positive neurites were observed normally in the spinal ventral horn of aged rats. After distal axotomy, without apparent neurodegeneration such as cell loss and decreased ChaT-immunoreactivity, increased levels of APP expression were observed in the spinal cords of aged rats post-injury. In contrast, after avulsion, expression of APP and A/, were downregulated in the spinal ventral horn of aged rats, and marked loss of spinal motor neurons and downregulated ChaT expression were observed. Our data indicate that APP and A/, might play beneficial roles in neuronal survival of aged spinal motor neurons after axonal injury. © 2003 Wiley-Liss, Inc. [source] Expression of the ETS transcription factor ER81 in the developing chick and mouse hindbrainDEVELOPMENTAL DYNAMICS, Issue 3 2002Yan Zhu Abstract ER81 is an ETS domain-containing transcription factor, which is expressed in various developing tissues and organs of the embryo and in pools of developing spinal motor neurons and proprioceptive sensory neurons. Analysis of mice lacking ER81 function showed that this gene played an important role in the establishment of sensory-motor circuitry in the spinal cord. Here, we investigate the expression pattern of er81 in the hindbrain of both chick and mouse embryos. We find that er81 is expressed in a subpopulation of inferior olive neurons, which send their projections to the caudal cerebellum. © 2002 Wiley-Liss, Inc. [source] Accelerated neuritogenesis and maturation of primary spinal motor neurons in response to nanofibersDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2010Caitlyn C. Gertz Abstract Neuritogenesis, neuronal polarity formation, and maturation of axons and dendrites are strongly influenced by both biochemical and topographical extracellular components. The aim of this study was to elucidate the effects of polylactic acid electrospun fiber topography on primary motor neuron development, because regeneration of motor axons is extremely limited in the central nervous system and could potentially benefit from the implementation of a synthetic scaffold to encourage regrowth. In this analysis, we found that both aligned and randomly oriented submicron fibers significantly accelerated the processes of neuritogenesis and polarity formation of individual cultured motor neurons compared to flat polymer films and glass controls, likely due to restricted lamellipodia formation observed on fibers. In contrast, dendritic maturation and soma spreading were inhibited on fiber substrates after 2 days in vitro. This study is the first to examine the effects of electrospun fiber topography on motor neuron neuritogenesis and polarity formation. Aligned nanofibers were shown to affect the directionality and timing of motor neuron development, providing further evidence for the effective use of electrospun scaffolds in neural regeneration applications. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 589,603, 2010 [source] A semaphorin code defines subpopulations of spinal motor neurons during mouse developmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005Samia Cohen Abstract In the spinal cord, motor neurons (MNs) with similar muscle targets and sensory inputs are grouped together into motor pools. To date, relatively little is known about the molecular mechanisms that control the establishment of pool-specific circuitry. Semaphorins, a large family of secreted and cell surface proteins, are important mediators of developmental processes such as axon guidance and cell migration. Here, we used mRNA in situ hybridization to study the expression patterns of semaphorins and their receptors, neuropilins and plexins, in the embryonic mouse spinal cord. Our data show that semaphorins and their receptors are differentially expressed in MNs that lie in distinct locations within the spinal cord. Furthermore, we report a combinatorial expression of class 3 (secreted) semaphorins and their receptors that characterizes distinct motor pools within the brachial and lumbar spinal cord. Finally, we found that a secreted semaphorin, Sema3A, elicits differential collapse responses in topologically distinct subpopulations of spinal MNs. These findings lead us to propose that semaphorins and their receptors might play important roles in the sorting of motor pools and the patterning of their afferent and efferent projections. [source] Generation of spinal motor neurons from human fetal brain-derived neural stem cells: Role of basic fibroblast growth factorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Paivi M. Jordan Abstract 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. bFGF induces NSCs to express the motor neuron marker Hb9, which is blocked by specific FGF receptor inhibitors and bFGF neutralizing antibodies. This development of spinal motor neuron properties is independent of selective proliferation or survival and does not require high levels of MAPK activation. Thus our study indicates that bFGF can play an important role in modulating plasticity and neuronal fate of human NSCs and presumably has implications for exploring the full potential of brain NSCs for clinical applications, particularly in spinal motor neuron regeneration. © 2008 Wiley-Liss, Inc. [source] Phosphorylation of the nicotinic acetylcholine receptor in myotube-cholinergic neuron coculturesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2006Maria A. Lanuza Abstract Acetylcholine receptor (AChR) stability in the postsynaptic membrane is affected by serine kinases. AChR are phosphorylated by protein kinase C (PKC) and PKA, and we have shown that activation of PKA and PKC have opposite effects on AChR stability and that this may play some role in the selective, activity-dependent synapse loss that occurs during development of the neuromuscular junction. Myotube cultures with and without added spinal motor neurons were probed with immunoaffinity-purified antibodies prepared against phosphorylated peptides with amino acid sequences from different AChR subunits. Different treatments activating PKC (phorbol 12-myristate 13-acetate; PMA) or PKA (dibutyryl cyclic adenosine monophosphate; cAMP) or blocking electrical activity (tetrodotoxin; TTX) of the cocultures were chosen because of their known effects, direct or indirect, on receptor stability. We asked whether the phospho-specific antibody staining in conjunction with ,-bungarotoxin (BTX) identification of AChR aggregates could provide a direct demonstration of changes in receptor phosphorylation produced by the treatments. We found that PMA treatment did increase phosphorylation of the delta subunit and cAMP increased phosphorylation of the epsilon subunit relative to total BTX labeling in muscle-nerve cocultures, but not in muscle-only cultures. Blockade of electrical activity with TTX increased the incidence of aggregates that showed no phospho-epsilon staining. Myotube cultures grown in the absence of neurons did not show the responses of myotubes in cocultures. The results show that manipulations that alter receptor stability also produce changes in receptor phosphorylation. We suggest that phosphorylation may be a mechanism mediating the changes in receptor stability. © 2006 Wiley-Liss, Inc. [source] Disease progression of human SOD1 (G93A) transgenic ALS model ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Arifumi Matsumoto Abstract The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies. © 2005 Wiley-Liss, Inc. [source] Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2005Hisashi Narai Abstract The role of insulin-like growth factor-1 (IGF-1) in amyotrophic lateral sclerosis (ALS) and its mechanism of action are important from both pathogenic and therapeutic points of view. The present study investigated the changes of IGF-1R, and the key intracellular downstream protein insulin receptor substrate-1 (IRS-1) by using SOD1G93A transgenic mice with continuous intrathecal IGF-1 treatment. The number of lumbar spinal motor neurons was preserved with IGF-1 treatment in a dose-dependent manner. The numbers of immunopositive motor neurons for IGF-1R, and IRS-1 were not significantly different between wild-type and Tg mice with vehicle treatment, whereas treatment of Tg mice with IGF-1 decreased the numbers of immunopositive motor neurons in a dose-dependent manner. On the other hand, the ratio of immunopositive motor neurons per total living motor neurons in vehicle-treated mice was greatly increased in Tg mice with vehicle treatment compared with wild-type mice. With IGF-1 treatment, the ratio was dramatically decreased in a dose-dependent manner. These results suggest that IGF-1 treatment prevents motor neuron loss by affecting the signal transduction system through IGF-1R and the main downstream signal, IRS-1. © 2005 Wiley-Liss, Inc. [source] Potential roles of Alzheimer precursor protein A4 and ,-amyloid in survival and function of aged spinal motor neurons after axonal injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Yuanyun Xie Abstract To study the potential role of Alzheimer precursor protein A4 (APP) and ,-amyloid (A/,) on aging motor neuron survival, expression of APP, A/,, and choline acetyltransferase (ChaT) were investigated in aged rats after either distal axotomy or root avulsion injury. Approximately 45% in number of total aged spinal motor neuron were normally APP-positive. A/,-positive neurites were observed normally in the spinal ventral horn of aged rats. After distal axotomy, without apparent neurodegeneration such as cell loss and decreased ChaT-immunoreactivity, increased levels of APP expression were observed in the spinal cords of aged rats post-injury. In contrast, after avulsion, expression of APP and A/, were downregulated in the spinal ventral horn of aged rats, and marked loss of spinal motor neurons and downregulated ChaT expression were observed. Our data indicate that APP and A/, might play beneficial roles in neuronal survival of aged spinal motor neurons after axonal injury. © 2003 Wiley-Liss, Inc. [source] 14-3-3 protein in the CSF of inflammatory peripheral neuropathiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004A Bersano 14-3-3 proteins are a highly conserved protein family of unknown function, although some authors suggested a role in cellular proliferation and differentiation, neurotransmitters biosynthesis and apoptosis. The expression of these proteins increases during development, in particular, in large projection neurons such as spinal motor neurons. Recently the protein was described in cerebrospinal fluid (CSF) of patients with spongiform encephalopathies, in particular Creutzfeld-Jacob disease, where the protein is considered a highly sensitive and specific marker. 14-3-3 protein has been also detected in CSF of other prion-unrelated dementias and other neurodegenerative (Parkinson disease, stroke and paraneoplastic syndromes) and inflammatory diseases like Multiple Sclerosis. The aim of our study was to evaluate whether the 14-3-3 protein is also present in the CSF of peripheral nervous system diseases. We studied by Western Blot the CSF of 120 patients including 38 with Guillain-Barré syndrome (GBS), 23 with chronic inflammatory demyelinating polyneuropathy (CIDP), 12 with multifocal motor neuropathies (MMN), 20 motor neuron disease (MND), 8 paraneoplastic syndrome, 14 other neuropathies or radiculopathies (OPN), and 5 normal subjects (NC). We found the 14-3-3 protein in the CSF of 21 (55%) patients with GBS, 13 (56%) with CIDP, 1 (5%) with MND, 3 (21%) with OPN and none with paraneoplastic syndrome, MMN or NC. Our results reveal that 14-3-3 protein can be detected not only in central but also in peripheral nervous system diseases where it is significantly associated (p < 0.0001) with GBS and CIDP. [source] Involvement of spinal motor neurons in parkin-positive autosomal recessive juvenile parkinsonismNEUROPATHOLOGY, Issue 1 2008Shoichi Sasaki We intensively examined the spinal cord of an autosomal recessive juvenile parkinsonism (ARJP) female patient with a homozygous exon 3 deletion in the parkin gene, anticipating a possible involvement of anterior horn neurons. Although the clinical features of the patient were consistent with parkinsonism as a result of parkin mutation, her tendon reflex was abolished in the lower limbs. This feature was in contrast with hyperreflexia, usually found in previous reports of ARJP. Histologically, on the level of the cervical, thoracic, and sacral spinal cord, anterior horn neurons were well preserved and normal. However, the lumbar spinal cord exhibited many swellings of proximal axons (spheroids) and degenerative changes in the somata of the large anterior horn neurons such as central chromatolysis, cystatin C-negative small eosinophilic inclusions, and eosinophilic Lewy body-like inclusions. Ultrastructurally, accumulations of neurofilaments and abnormal structures, such as inclusion bodies similar to skein-like inclusions and disorganized rough endoplasmic reticulum, were observed in the somata and neuronal processes. Lewy body-like inclusions in this study were positively immunostained for both ,-synuclein and ubiquitin that closely resemble Lewy bodies, but are different from Lewy body-like inclusions negatively immunostained for ,-synuclein in amyotrophic lateral sclerosis. These findings suggest that eosinophilic inclusions that closely resemble Lewy bodies may be formed in the spinal motor neurons of ARJP patients with parkin mutations and the motor neurons of these patients may be vulnerable to neurodegeneration. [source] Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis,ANNALS OF NEUROLOGY, Issue 3 2009Johannes Vogt MD Objective Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Methods We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high-precision stereology. Results Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor,related apoptosis-inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL-deficient T lymphocytes. Interpretation Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology. Ann Neurol 2009;66:310,332 [source] Protein kinase C, mediates ethanol withdrawal hyper-responsiveness of NMDA receptor currents in spinal cord motor neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2005Hui-Fang Li 1The present studies were designed to test the hypothesis that neuronal-specific protein kinase C, (PKC,) plays a critical role in acute ethanol withdrawal hyper-responsiveness in spinal cord. 2Patch-clamp studies were carried out in motor neurons in neonatal rat spinal cord slices. Postsynaptic currents were evoked by brief pulses of 2 mMN -methyl- D -aspartic acid (NMDA) in the presence of bicuculline methiodide 10 ,M; strychnine 5 ,M and tetrodotoxin 0.5 ,M. 3Both ethanol depression and withdrawal hyper-responsiveness of NMDA-evoked currents are dependent on increases in intracellular Ca2+. Blocking intracellular increase in Ca2+ by 30 mM 1,2-bis(2-aminophenoxy)-ethane- N,N,N,,N,-tetraacetic acid (BAPTA) not only decreased the ethanol-induced depression of NMDA-evoked currents (33±5% in control vs 20±3% in BAPTA, P<0.05) but also eliminated acute ethanol withdrawal hyper-responsiveness. 4Immunohistochemistry studies revealed that neonatal spinal cord motor neurons contain an abundance of nuclear PKC,. 5Exposure to ethanol (100 mM) induced PKC, translocation from the nucleus to cytoplasm in motor neurons. Pretreatment with the , -isozyme-specific peptide PKC inhibitor, ,V5-3, blocked ethanol-induced translocation and also blocked withdrawal hyper-responsiveness. 6The results show that PKC, mediates ethanol withdrawal hyper-responsiveness in spinal motor neurons; the results may be relevant to some symptoms of ethanol withdrawal in vivo. British Journal of Pharmacology (2005) 144, 301,307. doi:10.1038/sj.bjp.0706033 [source] | |||||||||||||