The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Richard Robitaille - One of the best experts on this subject based on the ideXlab platform.
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Purinergic-Dependent Glial Regulation of Synaptic Plasticity of Competing Terminals and Synapse Elimination at the Neuromuscular Junction
Elsevier, 2018Co-Authors: Houssam Darabid, Alexandre St-pierre-see, Richard RobitailleAbstract:Summary: The precise wiring of synaptic connections requires the elimination of supernumerary inputs competing for innervation of the same target cell. This competition is activity-dependent, strengthening some inputs whereas others are eliminated. Although glial Cells are required for the elimination and clearance of terminals, their involvement in activity-dependent synaptic competition remains ill-defined. Here, we used the developing neuromuscular junctions of mice to show that Perisynaptic glial Cells, through 2Y1 purinergic receptors (P2Y1Rs), decode synaptic efficacy of competing terminals in a Ca2+-dependent manner. This glial activity induces long-lasting synaptic potentiation of strong but not weak terminals via presynaptic adenosine 2A receptors. Blockade of glial activity by intracellular Ca2+ chelation or blockade of P2Y1Rs prevents this plasticity. In addition, blockade of P2Y1Rs delays synapse elimination in vivo. Hence, P2Y1Rs drive glial cell regulation of strong synaptic inputs and influence synapse competition and elimination. : Darabid et al. show that glial Cells at the neuromuscular synapse decode, in a purinergically dependent manner, the synaptic properties of nerve terminals competing for the same site. They then selectively strengthen the stronger input, which further favors its propensity to win the competition. Blockade of purinergic receptors delays synapse elimination in vivo. Keywords: synaptic competition, synapse elimination, Perisynaptic Schwann Cells, synaptic strength, synaptic plasticity, P2Y1 receptors, A2A receptor
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New perspectives on amyotrophic lateral sclerosis: the role of glial Cells at the neuromuscular junction
The Journal of physiology, 2016Co-Authors: Danielle Arbour, Christine Vande Velde, Richard RobitailleAbstract:Amyotrophic lateral sclerosis (ALS) is a disease leading to the death of motor neurons (MNs). It is also recognized as a non-cell autonomous disease where glial Cells in the CNS are involved in its pathogenesis and progression. However, although denervation of neuromuscular junctions (NMJs) represents an early and major event in ALS, the importance of glial Cells at this synapse receives little attention. An interesting possibility is that altered relationships between glial Cells and MNs in the spinal cord in ALS may also take place at the NMJ. Perisynaptic Schwann Cells (PSCs), which are glial Cells at the NMJ, show great morphological and functional adaptability to ensure NMJ stability, maintenance and repair. More specifically, PSCs change their properties according to the state of innervation. Hence, abnormal changes or lack of changes can have detrimental effects on NMJs in ALS. This review will provide an overview of known and hypothesized interactions between MN nerve terminals and PSCs at NMJs during development, aging and ALS-induced denervation. These neuron-PSC interactions may be crucial to the understanding of how degenerative changes begin and progress at NMJs in ALS, and represent a novel therapeutic target.
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Perisynaptic Schwann Cells at the Neuromuscular Synapse: Adaptable, Multitasking Glial Cells
Cold Spring Harbor perspectives in biology, 2015Co-Authors: Richard RobitailleAbstract:The neuromuscular junction (NMJ) is engineered to be a highly reliable synapse to carry the control of the motor commands of the nervous system over the muscles. Its development, organization, and synaptic properties are highly structured and regulated to support such reliability and efficacy. Yet, the NMJ is also highly plastic, able to react to injury and adapt to changes. This balance between structural stability and synaptic efficacy on one hand and structural plasticity and repair on another hand is made possible by the intricate regulation of Perisynaptic Schwann Cells, glial Cells at this synapse. They regulate both the efficacy and structural plasticity of the NMJ in a dynamic, bidirectional manner owing to their ability to decode synaptic transmission and by their interactions via trophic-related factors.
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Early and Persistent Abnormal Decoding by Glial Cells at the Neuromuscular Junction in an ALS Model
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015Co-Authors: Danielle Arbour, Elsa Tremblay, Eric Martineau, Jean-pierre Julien, Richard RobitailleAbstract:Amyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease characterized by progressive loss of motor neurons (MNs) preceded by neuromuscular junction (NMJ) denervation. Despite the importance of NMJ denervation in ALS, the mechanisms involved remain unexplored and ill defined. The contribution of glial Cells in the disease has been highlighted, including axonal Schwann cell activation that precedes the decline of motor function and the onset of hindlimb paralysis. Because NMJ denervation occurs early in the process and that Perisynaptic Schwann Cells (PSCs), glial Cells at the NMJ, regulate morphological stability, integrity, and repair of the NMJ, one could predict that PSC functions would be altered even before denervation, contributing to NMJ malfunctions. We tested this possibility using a slowly progressive model of ALS (SOD1G37R mice). We observed a normal NMJ organization at a presymptomatic stage of ALS (120 d), but PSC detection of endogenous synaptic activity revealed by intracellular Ca2+ changes was enhanced compared with their wild-type littermates. This inappropriate PSC decoding ability was associated with an increased level of neurotransmitter release and dependent on intrinsic glial properties related to enhanced muscarinic receptor activation. The alteration of PSC muscarinic receptor functions also persists during the preonset stage of the disease and became dependent on MN vulnerability with age. Together, these results suggest that PSC properties are altered in the disease process in a manner that would be detrimental for NMJ repair. The impairments of PSC functions may contribute to NMJ dysfunction and ALS pathogenesis.
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Neuromuscular synaptogenesis: coordinating partners with multiple functions
Nature Reviews Neuroscience, 2014Co-Authors: Houssam Darabid, Anna P. Perez-gonzalez, Richard RobitailleAbstract:Although it is fundamentally a simple synapse, the formation and maturation of the neuromuscular junction (NMJ) involves a complex molecular and activity-dependent crosstalk among presynaptic terminals, postsynaptic muscle fibres and glial Cells. This crosstalk results in the tight assembly of an efficient and reliable communication unit. The maturation of the NMJ involves precise and highly regulated molecular mechanisms. These mechanisms promote the clustering and stabilization of nicotinic acetylcholine receptors at the crest of postjunctional folds, as well as the differentiation of the presynaptic element to form active zones with proper synaptic proteins and clustered synaptic vesicles. Presynaptic and postsynaptic maturation are interdependent and coordinated by common molecular and regulatory mechanisms. Glial Cells also participate in synaptic maturation, which is dependent on both pre- and postsynaptic elements. The NMJ undergoes activity-dependent maturation, which involves a drastic reduction in the number of presynaptic terminals via synaptic competition. The superseding nerve terminal is the one that delivers the most efficient synaptic communication (the strongest input) and that is in the best position to benefit from interactions with the muscle fibre and glial Cells. Glial Cells at the NMJ regulate synaptic competition by clearing debris and participating in the elimination of supernumerary nerve terminals. They also actively decode the ongoing synaptic competition, discriminating competing inputs by detecting the levels of transmitter released from each competing nerve terminal. This enables these Cells to then actively enhance the synaptic properties of a particular input to promote its survival. The formation and maturation of the neuromuscular junction require the concerted efforts of the presynaptic nerve terminal, the postsynaptic muscle fibre and Perisynaptic Schwann Cells. In this Review, Robitaille and colleagues describe the molecular and activity-dependent processes that underlie the development of neuron–muscle contacts. The formation of highly efficient and reliable synapses at the neuromuscular junction (NMJ) relies on dynamic molecular interactions. Studies of the development and maturation of the NMJ have focused on events that are dependent on synaptic activity and that require the coordinated actions of nerve- and muscle-derived molecules with different targets and effects. More recently, Perisynaptic Schwann Cells — the glial Cells at NMJs — have become an important focus of research. These glia concomitantly contribute to pre- and postsynaptic maturation while undergoing maturation themselves. Thus, an intricate 'danse à trois' regulates the maturation of the NMJ to form a highly efficient communication unit, in which fine glial processes lie in close proximity to a highly concentrated population of postsynaptic receptors and perfectly aligned presynaptic release sites.
Samuele Negro - One of the best experts on this subject based on the ideXlab platform.
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CXCL12α/SDF-1 from Perisynaptic Schwann Cells promotes regeneration of injured motor axon terminals.
EMBO molecular medicine, 2017Co-Authors: Samuele Negro, Francesca Lessi, Elisa Duregotti, Paolo Aretini, Marco La Ferla, Sara Franceschi, Michele Menicagli, Elisanna Bergamin, Egle Radice, Marcus ThelenAbstract:Abstract The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by Perisynaptic Schwann Cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo . Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro . These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage.
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cxcl12α sdf 1 from Perisynaptic Schwann Cells promotes regeneration of injured motor axon terminals
Embo Molecular Medicine, 2017Co-Authors: Samuele Negro, Francesca Lessi, Elisa Duregotti, Paolo Aretini, Marco La Ferla, Sara Franceschi, Michele Menicagli, Elisanna Bergamin, Egle Radice, Marcus ThelenAbstract:Abstract The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by Perisynaptic Schwann Cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo . Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro . These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage.
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An animal model of Miller Fisher syndrome: Mitochondrial hydrogen peroxide is produced by the autoimmune attack of nerve terminals and activates Schwann Cells.
Neurobiology of disease, 2016Co-Authors: Umberto Rodella, Samuele Negro, Elisa Duregotti, Michele Scorzeto, Bryan C. Dickinson, Christopher J. Chang, Michela Rigoni, Nobuhiro Yuki, Cesare MontecuccoAbstract:The neuromuscular junction is a tripartite synapse composed of the presynaptic nerve terminal, the muscle and Perisynaptic Schwann Cells. Its functionality is essential for the execution of body movements and is compromised in a number of disorders, including Miller Fisher syndrome, a variant of Guillain-Barre syndrome: this autoimmune peripheral neuropathy is triggered by autoantibodies specific for the polysialogangliosides GQ1b and GT1a present in motor axon terminals, including those innervating ocular muscles, and in sensory neurons. Their binding to the presynaptic membrane activates the complement cascade, leading to a nerve degeneration that resembles that caused by some animal presynaptic neurotoxins. Here we have studied the intra- and inter-cellular signaling triggered by the binding and complement activation of a mouse monoclonal anti-GQ1b/GT1a antibody to primary cultures of spinal cord motor neurons and cerebellar granular neurons. We found that a membrane attack complex is rapidly assembled following antibody binding, leading to calcium accumulation, which affects mitochondrial functionality. Consequently, using fluorescent probes specific for mitochondrial hydrogen peroxide, we found that this reactive oxygen species is rapidly produced by mitochondria of damaged neurons, and that it triggers the activation of the MAP kinase pathway in Schwann Cells. These results throw light on the molecular and cellular pathogenesis of Miller Fisher syndrome, and may well be relevant to other pathologies of the motor axon terminals, including some subtypes of the Guillain Barre syndrome.
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ATP Released by Injured Neurons Activates Schwann Cells.
Frontiers in cellular neuroscience, 2016Co-Authors: Samuele Negro, Elisa Duregotti, Elisanna Bergamin, Michele Scorzeto, Cesare Montecucco, Umberto Rodella, Kees Jalink, Michela RigoniAbstract:Injured nerve terminals of neuromuscular junctions (NMJs) can regenerate. This remarkable and complex response is governed by molecular signals that are exchanged among the cellular components of this synapse: motor axon nerve terminal (MAT), Perisynaptic Schwann Cells (PSCs), and muscle fiber. The nature of signals that govern MAT regeneration is ill-known. In the present study the spider toxin α-latrotoxin has been used as tool to investigate the mechanisms underlying peripheral neuroregeneration. Indeed this neurotoxin induces an acute, specific, localized and fully reversible damage of the presynaptic nerve terminal, and its action mimics the cascade of events that leads to nerve terminal degeneration in injured patients and in many neurodegenerative conditions. Here we provide evidence of an early release by degenerating neurons of adenosine triphosphate as alarm messenger, that contributes to the activation of a series of intracellular pathways within Schwann Cells that are crucial for nerve regeneration: Ca(2+), cAMP, ERK1/2, and CREB. These results contribute to define the cross-talk taking place among degenerating nerve terminals and PSCs, involved in the functional recovery of the NMJ.
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Mitochondrial alarmins released by degenerating motor axon terminals activate Perisynaptic Schwann Cells
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Elisa Duregotti, Samuele Negro, Michele Scorzeto, Irene Zornetta, Bryan C. Dickinson, Christopher J. Chang, Cesare Montecucco, Michela RigoniAbstract:An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann Cells, Schwann Cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases.
Elisa Duregotti - One of the best experts on this subject based on the ideXlab platform.
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CXCL12α/SDF-1 from Perisynaptic Schwann Cells promotes regeneration of injured motor axon terminals.
EMBO molecular medicine, 2017Co-Authors: Samuele Negro, Francesca Lessi, Elisa Duregotti, Paolo Aretini, Marco La Ferla, Sara Franceschi, Michele Menicagli, Elisanna Bergamin, Egle Radice, Marcus ThelenAbstract:Abstract The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by Perisynaptic Schwann Cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo . Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro . These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage.
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cxcl12α sdf 1 from Perisynaptic Schwann Cells promotes regeneration of injured motor axon terminals
Embo Molecular Medicine, 2017Co-Authors: Samuele Negro, Francesca Lessi, Elisa Duregotti, Paolo Aretini, Marco La Ferla, Sara Franceschi, Michele Menicagli, Elisanna Bergamin, Egle Radice, Marcus ThelenAbstract:Abstract The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by Perisynaptic Schwann Cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo . Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro . These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage.
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An animal model of Miller Fisher syndrome: Mitochondrial hydrogen peroxide is produced by the autoimmune attack of nerve terminals and activates Schwann Cells.
Neurobiology of disease, 2016Co-Authors: Umberto Rodella, Samuele Negro, Elisa Duregotti, Michele Scorzeto, Bryan C. Dickinson, Christopher J. Chang, Michela Rigoni, Nobuhiro Yuki, Cesare MontecuccoAbstract:The neuromuscular junction is a tripartite synapse composed of the presynaptic nerve terminal, the muscle and Perisynaptic Schwann Cells. Its functionality is essential for the execution of body movements and is compromised in a number of disorders, including Miller Fisher syndrome, a variant of Guillain-Barre syndrome: this autoimmune peripheral neuropathy is triggered by autoantibodies specific for the polysialogangliosides GQ1b and GT1a present in motor axon terminals, including those innervating ocular muscles, and in sensory neurons. Their binding to the presynaptic membrane activates the complement cascade, leading to a nerve degeneration that resembles that caused by some animal presynaptic neurotoxins. Here we have studied the intra- and inter-cellular signaling triggered by the binding and complement activation of a mouse monoclonal anti-GQ1b/GT1a antibody to primary cultures of spinal cord motor neurons and cerebellar granular neurons. We found that a membrane attack complex is rapidly assembled following antibody binding, leading to calcium accumulation, which affects mitochondrial functionality. Consequently, using fluorescent probes specific for mitochondrial hydrogen peroxide, we found that this reactive oxygen species is rapidly produced by mitochondria of damaged neurons, and that it triggers the activation of the MAP kinase pathway in Schwann Cells. These results throw light on the molecular and cellular pathogenesis of Miller Fisher syndrome, and may well be relevant to other pathologies of the motor axon terminals, including some subtypes of the Guillain Barre syndrome.
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ATP Released by Injured Neurons Activates Schwann Cells.
Frontiers in cellular neuroscience, 2016Co-Authors: Samuele Negro, Elisa Duregotti, Elisanna Bergamin, Michele Scorzeto, Cesare Montecucco, Umberto Rodella, Kees Jalink, Michela RigoniAbstract:Injured nerve terminals of neuromuscular junctions (NMJs) can regenerate. This remarkable and complex response is governed by molecular signals that are exchanged among the cellular components of this synapse: motor axon nerve terminal (MAT), Perisynaptic Schwann Cells (PSCs), and muscle fiber. The nature of signals that govern MAT regeneration is ill-known. In the present study the spider toxin α-latrotoxin has been used as tool to investigate the mechanisms underlying peripheral neuroregeneration. Indeed this neurotoxin induces an acute, specific, localized and fully reversible damage of the presynaptic nerve terminal, and its action mimics the cascade of events that leads to nerve terminal degeneration in injured patients and in many neurodegenerative conditions. Here we provide evidence of an early release by degenerating neurons of adenosine triphosphate as alarm messenger, that contributes to the activation of a series of intracellular pathways within Schwann Cells that are crucial for nerve regeneration: Ca(2+), cAMP, ERK1/2, and CREB. These results contribute to define the cross-talk taking place among degenerating nerve terminals and PSCs, involved in the functional recovery of the NMJ.
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Mitochondrial alarmins released by degenerating motor axon terminals activate Perisynaptic Schwann Cells
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Elisa Duregotti, Samuele Negro, Michele Scorzeto, Irene Zornetta, Bryan C. Dickinson, Christopher J. Chang, Cesare Montecucco, Michela RigoniAbstract:An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann Cells, Schwann Cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases.
Emily K. Mathey - One of the best experts on this subject based on the ideXlab platform.
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Clinical implications of Schwann cell biology
Journal of The Peripheral Nervous System, 2014Co-Authors: Patricia J. Armati, Emily K. MatheyAbstract:The neuroglia of the peripheral nervous system (PNS) are derived from the neural crest and are a diverse family of Cells. They consist of myelinating Schwann Cells, non-myelinating Schwann Cells, satellite Cells, and Perisynaptic Schwann Cells. Due to their prominent role in the formation of myelin, myelinating Schwann Cells are the best recognised of these Cells. However, Schwann Cells and the other neuroglia of the PNS have many functions that are independent of myelination and contribute significantly to the functioning of the peripheral nerve in both health and disease. Here we discuss the contribution of PNS neuroglial Cells to clinical deficit in neurodegenerative disease, peripheral neuropathy, and pain.
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An update on Schwann cell biology--immunomodulation, neural regulation and other surprises.
Journal of the neurological sciences, 2013Co-Authors: Patricia J. Armati, Emily K. MatheyAbstract:Schwann Cells are primarily discussed in the context of their ability to form myelin. However there are many subtypes of these neural crest derived Cells including satellite Cells of the dorsal root ganglia and autonomic ganglia, the Perisynaptic Schwann Cells of the neuromuscular junction and the non-myelin forming Schwann Cells which ensheathe the unmyelinated fibres of the peripheral nervous system which are about 80% of peripheral nerves. This review discusses the many functions of these Schwann cell subsets including their seminal role in axonal ensheathment, perineuronal organisation, maintenance of normal neural function, synapse formation, response to damage and repair and an increasingly recognised active role in pain syndromes.
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An update on Schwann cell biology — Immunomodulation, neural regulation and other surprises
Journal of the Neurological Sciences, 2013Co-Authors: Patricia J. Armati, Emily K. MatheyAbstract:Schwann Cells are primarily discussed in the context of their ability to form myelin. However there are many subtypes of these neural crest derived Cells including satellite Cells of the dorsal root ganglia and autonomic ganglia, the Perisynaptic Schwann Cells of the neuromuscular junction and the non-myelin forming Schwann Cells which ensheathe the unmyelinated fibres of the peripheral nervous system which are about 80% of peripheral nerves. This review discusses the many functions of these Schwann cell subsets including their seminal role in axonal ensheathment, perineuronal organisation, maintenance of normal neural function, synapse formation, response to damage and repair and an increasingly recognised active role in pain syndromes.
Z. Feng - One of the best experts on this subject based on the ideXlab platform.
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Schwann Cells and Plasticity of the Neuromuscular Junction
Encyclopedia of Neuroscience, 2009Co-Authors: Z. FengAbstract:The neuromuscular junction (NMJ) is composed of three cellular elements: the presynaptic nerve terminal, the postsynaptic specialization, and Perisynaptic Schwann Cells (PSCs; also called terminal Schwann Cells). In developing muscles, PSCs guide extending nerve terminals and promote synaptic growth and maintenance. In adult muscles, PSCs play an essential role in the long-term maintenance of synaptic structure and function. PSC sprouts lead nerve terminal sprouts during synaptic remodeling in intact muscles. After nerve injury, PSCs sprout extensive processes, which also guide regenerating nerve terminals. Thus, PSCs play multiple roles in the plasticity of the vertebrate NMJ, and should be considered as an active and integral partner of the tripartite synapse.
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The role of glial Cells in the formation and maintenance of the neuromuscular junction.
Annals of the New York Academy of Sciences, 2008Co-Authors: Z. FengAbstract:The vertebrate neuromuscular junction (NMJ) is a "tripartite" synapse, composed of three cellular elements: the presynaptic nerve terminal, the postsynaptic specialization, and synapse-associated glial Cells, called Perisynaptic Schwann Cells (PSCs; also called terminal Schwann Cells). During development, PSCs grow beyond nerve terminals and guide nerve terminal extension. Nerve terminals retract or stop extension after PSC ablation by complement-mediated lysis in vivo, suggesting that PSCs can promote synaptic growth and maintenance at developing NMJs. Schwann cell-conditioned medium (SC-CM), which may be mediated by transforming growth factor-beta1, can promote synapse formation in Xenopus nerve-muscle culture. In addition, SC-CM contains small molecules (within 500-5000 Da), which can enhance spontaneous synaptic activities acutely and potently at developing frog NMJs. In adult muscles, PSCs can detect evoked synaptic activities and are capable of modulating transmitter release. Nerve terminals retract and synaptic efficacy is reduced at 1 week, but not within the first few hours, after PSC ablation. Thus, PSCs are essential for the long-term, but not short-term, maintenance of synaptic structure and function at the adult NMJ. During synaptic remodeling in adult muscles, PSC sprouts lead nerve terminal sprouts. After nerve injury, adult PSCs sprout extensive processes, which guide regenerating nerve terminals. Schwann Cells express agrin and neuregulins, which may help the postsynaptic differentiation and synaptic repair. Furthermore, neuregulin-ErbB signaling pathways play an essential role in synapse-glial interactions at the NMJ. These recent findings suggest that PSCs play multiple roles and actively participate in synaptic development, modulation, maintenance, and repair of the vertebrate NMJ.
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Neuronal glia interactions at the vertebrate neuromuscular junction.
Current opinion in pharmacology, 2007Co-Authors: Z. FengAbstract:Emerging studies demonstrate that Perisynaptic Schwann Cells (PSCs), which are the glia Cells juxtaposed to the motor nerve terminal, actively participate in multiple aspects of the neuromuscular junction. During development, PSCs guide and promote synaptic growth. In adult muscles, PSCs can sense nerve stimulation by increasing intracellular calcium and are also capable of modulating transmitter release. Although adult PSCs are not required for acute synaptic maintenance and function, they are indispensable for long-term synaptic maintenance. Furthermore, PSC sprouts lead nerve terminal extension during synaptic remodeling. After nerve injury, PSCs sprout profusely and PSC processes guide regenerating nerve terminals. Future challenges will be to identify the molecular mechanisms by which PSCs interact with the nerve terminal and the muscle fiber.
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Synapse-Glia Interactions at the Vertebrate Neuromuscular Junction:
The Neuroscientist : a review journal bringing neurobiology neurology and psychiatry, 2005Co-Authors: Z. Feng, Samir KoiralaAbstract:Glial Cells are widely distributed throughout the nervous system, including at the chemical synapse. However, our knowledge of the role of glial Cells at the synapse is rudimentary. Recent studies using a model synapse, the vertebrate neuromuscular junction (NMJ), have demonstrated that Perisynaptic Schwann Cells (PSCs), which are the glia juxtaposed to the nerve terminal at the NMJ, play active and essential roles in synaptic function, maintenance, and development. PSCs can respond to nerve activity by increasing intracellular calcium and are capable of modulating synaptic function in response to pharmacological manipulations. Studies using PSC ablation in vivo have shown that PSCs are essential for the long-term maintenance of synaptic structure and function at the adult NMJ. In vivo observations have also shown that PSCs guide presynaptic nerve terminal extension and dictate the pattern of innervation during synaptic regeneration and remodeling at adult NMJs. PSCs may also induce postsynaptic acetylcholine receptor aggregation. Furthermore, PSCs play an essential role in synaptic growth and maintenance during development of NMJs in vivo, and Schwann cell-derived factors can promote synaptogenesis and enhance synaptic transmission in tissue culture. These recent findings advance the emerging concept that glial Cells help make bigger, stronger, and more stable synapses.