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Jaap J Plomp - One of the best experts on this subject based on the ideXlab platform.
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the pre synaptic motor Nerve Terminal as a site for antibody mediated neurotoxicity in autoimmune neuropathies and synaptopathies
Journal of Anatomy, 2014Co-Authors: Simon N Fewou, Jaap J Plomp, Hugh J. WillisonAbstract:The pre-synaptic motor Nerve Terminal is a highly complex and dynamic compartment within the lower motor neuron responsible for converting electrical signals into secreted chemicals. This self-renewing process of synaptic transmission is accomplished by the calcium-triggered fusion of neurotransmitter-containing vesicles with the plasma membrane and the subsequent retrieval and recycling of vesicle components. Besides this conventional physiological role, the highly active process of vesicle fusion and re-uptake into endosomal sorting pathways acts as a conduit for entry of a range of substances into the intracellular compartment of the motor Nerve Terminal. Whilst this entry portal sub-serves many vital physiological processes, such as those mediated by neurotrophin trafficking, there is also the potential for substantial pathological consequences resulting from uptake of noxious agents, including autoantibodies, viruses and toxins. These may act locally to induce disease within the Nerve Terminal, or traffic beyond to the motor neuron cell body and central nervous system to exert their pathological effects. This review focuses on the recent evidence that the ganglioside-rich pre-synaptic membrane acts as a binding site for potentially neurotoxic serum autoantibodies that are present in human autoimmune motor neuropathies. Autoantibodies that bind surface antigens induce membrane lytic effects, whereas their uptake attenuates local injury and transfers any potential pathological consequences to the intracellular compartment. Herein the thesis is explored that a balance exists between local injury at the exofacial leaflet of the pre-synaptic membrane and antibody uptake, which dictates the overall level and site of motor Nerve injury in this group of disorders.
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anti ganglioside antibody internalization attenuates motor Nerve Terminal injury in a mouse model of acute motor axonal neuropathy
Journal of Clinical Investigation, 2012Co-Authors: Simon N Fewou, Angie Rupp, Kay N. Greenshields, Jaap J Plomp, Lauren E Nickolay, Kathryn Carrick, John D Pediani, Hugh J. WillisonAbstract:In the Guillain-Barre syndrome subform acute motor axonal neuropathy (AMAN), Campylobacter jejuni enteritis triggers the production of anti-ganglioside Abs (AGAbs), leading to immune-mediated injury of distal motor Nerves. An important question has been whether injury to the presynaptic neuron at the neuromuscular junction is a major factor in AMAN. Although disease modeling in mice exposed to AGAbs indicates that complement-mediated necrosis occurs extensively in the presynaptic axons, evidence in humans is more limited, in comparison to the extensive injury seen at nodes of Ranvier. We considered that rapid AGAb uptake at the motor Nerve Terminal membrane might attenuate complement-mediated injury. We found that PC12 rat neuronal cells rapidly internalized AGAb, which were trafficked to recycling endosomes and lysosomes. Consequently, complement-mediated cytotoxicity was attenuated. Importantly, we observed the same AGAb endocytosis and protection from cytotoxicity in live mouse Nerve Terminals. AGAb uptake was attenuated following membrane cholesterol depletion in vitro and ex vivo, indicating that this process may be dependent upon cholesterol-enriched microdomains. In contrast, we observed minimal AGAb uptake at nodes of Ranvier, and this structure thus remained vulnerable to complement-mediated injury. These results indicate that differential endocytic processing of AGAbs by different neuronal and glial membranes might be an important modulator of site-specific injury in acute AGAb-mediated Guillain-Barre syndrome subforms and their chronic counterparts.
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the role of complement and complement regulators in mediating motor Nerve Terminal injury in murine models of guillain barre syndrome
Journal of Neuroimmunology, 2008Co-Authors: Hugh J. Willison, Susan K Halstead, Kay N. Greenshields, Erin Beveridge, Femke M P Zitman, Paul B Morgan, Jaap J PlompAbstract:Recent research into the Guillain-Barre syndromes (GBS) has focused on anti-ganglioside antibodies that correlate with specific clinical phenotypes. Our increasing understanding of the role of antibodies in mediating GBS has naturally focused our attention on complement involvement in the pathological procession. We have studied the axonal and glial components of the murine motor Nerve Terminal as a model site of antibody and complement mediated injury. Such studies are providing us with clear information on the molecular components underlying our clinicopathological model for GBS and have lead us to the testing of emerging complement therapeutics that are potentially suitable for human use.
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Anti-ganglioside antibodies and the presynaptic motor Nerve Terminal.
Annals of the New York Academy of Sciences, 2008Co-Authors: Hugh J. Willison, Jaap J PlompAbstract:The Guillain Barre syndromes (GBS) are the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the pathophysiological events of GBS, and improving immunotherapies are fundamental to improving the clinical outcome. Recent research into GBS and the Miller Fisher syndrome (MFS) variant has focused on the forms mediated by anti-ganglioside antibodies in which correlations have been established between anti-ganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/GD1a antibodies and the acute motor axonal variant and anti-GQ1b/GT1a antibodies and MFS. Anti-ganglioside antibodies can arise through molecular mimicry with GBS-associated Campylobacter jejuni oligosaccharides. Our work has focused on axonal and glial components of the motor Nerve Terminal as a model site of injury, and through combined active and passive immunization paradigms in glycosyltransferase knockout mice we have developed murine neuropathy phenotypes mediated by anti-ganglioside antibodies. Several determinants influence disease expression including the level of immunological tolerance to microbial glycans that mimic self gangliosides, the degree of complement activation, and the ganglioside density in target tissue. Such studies provide us with clear information on an antibody-mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in man.
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Calpain inhibitors protect against axonal degeneration in a model of anti-ganglioside antibody-mediated motor Nerve Terminal injury.
Brain, 2003Co-Authors: Graham M. O'hanlon, Susan K Halstead, Peter D Humphreys, Jaap J Plomp, Rebecca S Goldman, Roland W M Bullens, Yuri Ushkaryov, Hugh J. WillisonAbstract:Summary Miller Fisher syndrome-associated anti-GQ1b ganglioside antibodies produce an acute complement-dependent neuroexocytic effect at the mouse neuromuscular junction (NMJ) that closely resembles the effect of a-latrotoxin (LTx). This pathophysiological effect is accompanied by morphological disruption of the Nerve Terminal involving the loss of major cytoskeletal components, including neurofilament. Both LTx and the membrane attack complex of complement form membrane pores that allow free ionic movement and we have previously hypothesized that Ca 2+ ingress and the subsequent activation of Ca 2+ -dependent proteases, cal
Hugh J. Willison - One of the best experts on this subject based on the ideXlab platform.
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The Effects of Age and Ganglioside Composition on the Rate of Motor Nerve Terminal Regeneration Following Antibody-Mediated Injury in Mice
2016Co-Authors: Angie Rupp, Koichi Furukawa, Madeleine E. Cunningham, Denggao Yao, Hugh J. WillisonAbstract:KEY WORDS antibody; complement; ganglioside; neuromuscular junction; neuropathy ABSTRACT Gangliosides are glycosphingolipids highly enriched in neural plasma membranes, where they mediate a diverse range of functions and can act as targets for auto-antibodies present in human immune-mediated neuropathy sera. The ensuing autoimmune injury results in axonal and motor Nerve Terminal (mNT) degeneration. Both aging and ganglioside-deficiency have been linked to impaired axonal regenera-tion. To assess the effects of age and ganglioside expression on mNT regeneration in an autoimmune injury paradigm, anti-ganglioside antibodies and complement were applied to young adult and aged mice wildtype (WT) mice, mice deficient in either b-and c-series (GD3sKO) or mice deficient in all complex gangliosides (GM2sKO). The extent of mNT injury and regeneration was assessed immediately or after 5 days, respectively. Depending on ganglioside expression and antibody-specificity, either a selective mNT injury or a combined injury of mNTs and neuromuscular glial cells was elicited. Immediately after induction of the injury, between 1.5 % and 11.8 % of neuro
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the pre synaptic motor Nerve Terminal as a site for antibody mediated neurotoxicity in autoimmune neuropathies and synaptopathies
Journal of Anatomy, 2014Co-Authors: Simon N Fewou, Jaap J Plomp, Hugh J. WillisonAbstract:The pre-synaptic motor Nerve Terminal is a highly complex and dynamic compartment within the lower motor neuron responsible for converting electrical signals into secreted chemicals. This self-renewing process of synaptic transmission is accomplished by the calcium-triggered fusion of neurotransmitter-containing vesicles with the plasma membrane and the subsequent retrieval and recycling of vesicle components. Besides this conventional physiological role, the highly active process of vesicle fusion and re-uptake into endosomal sorting pathways acts as a conduit for entry of a range of substances into the intracellular compartment of the motor Nerve Terminal. Whilst this entry portal sub-serves many vital physiological processes, such as those mediated by neurotrophin trafficking, there is also the potential for substantial pathological consequences resulting from uptake of noxious agents, including autoantibodies, viruses and toxins. These may act locally to induce disease within the Nerve Terminal, or traffic beyond to the motor neuron cell body and central nervous system to exert their pathological effects. This review focuses on the recent evidence that the ganglioside-rich pre-synaptic membrane acts as a binding site for potentially neurotoxic serum autoantibodies that are present in human autoimmune motor neuropathies. Autoantibodies that bind surface antigens induce membrane lytic effects, whereas their uptake attenuates local injury and transfers any potential pathological consequences to the intracellular compartment. Herein the thesis is explored that a balance exists between local injury at the exofacial leaflet of the pre-synaptic membrane and antibody uptake, which dictates the overall level and site of motor Nerve injury in this group of disorders.
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anti ganglioside antibody internalization attenuates motor Nerve Terminal injury in a mouse model of acute motor axonal neuropathy
Journal of Clinical Investigation, 2012Co-Authors: Simon N Fewou, Angie Rupp, Kay N. Greenshields, Jaap J Plomp, Lauren E Nickolay, Kathryn Carrick, John D Pediani, Hugh J. WillisonAbstract:In the Guillain-Barre syndrome subform acute motor axonal neuropathy (AMAN), Campylobacter jejuni enteritis triggers the production of anti-ganglioside Abs (AGAbs), leading to immune-mediated injury of distal motor Nerves. An important question has been whether injury to the presynaptic neuron at the neuromuscular junction is a major factor in AMAN. Although disease modeling in mice exposed to AGAbs indicates that complement-mediated necrosis occurs extensively in the presynaptic axons, evidence in humans is more limited, in comparison to the extensive injury seen at nodes of Ranvier. We considered that rapid AGAb uptake at the motor Nerve Terminal membrane might attenuate complement-mediated injury. We found that PC12 rat neuronal cells rapidly internalized AGAb, which were trafficked to recycling endosomes and lysosomes. Consequently, complement-mediated cytotoxicity was attenuated. Importantly, we observed the same AGAb endocytosis and protection from cytotoxicity in live mouse Nerve Terminals. AGAb uptake was attenuated following membrane cholesterol depletion in vitro and ex vivo, indicating that this process may be dependent upon cholesterol-enriched microdomains. In contrast, we observed minimal AGAb uptake at nodes of Ranvier, and this structure thus remained vulnerable to complement-mediated injury. These results indicate that differential endocytic processing of AGAbs by different neuronal and glial membranes might be an important modulator of site-specific injury in acute AGAb-mediated Guillain-Barre syndrome subforms and their chronic counterparts.
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the role of complement and complement regulators in mediating motor Nerve Terminal injury in murine models of guillain barre syndrome
Journal of Neuroimmunology, 2008Co-Authors: Hugh J. Willison, Susan K Halstead, Kay N. Greenshields, Erin Beveridge, Femke M P Zitman, Paul B Morgan, Jaap J PlompAbstract:Recent research into the Guillain-Barre syndromes (GBS) has focused on anti-ganglioside antibodies that correlate with specific clinical phenotypes. Our increasing understanding of the role of antibodies in mediating GBS has naturally focused our attention on complement involvement in the pathological procession. We have studied the axonal and glial components of the murine motor Nerve Terminal as a model site of antibody and complement mediated injury. Such studies are providing us with clear information on the molecular components underlying our clinicopathological model for GBS and have lead us to the testing of emerging complement therapeutics that are potentially suitable for human use.
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Anti-ganglioside antibodies and the presynaptic motor Nerve Terminal.
Annals of the New York Academy of Sciences, 2008Co-Authors: Hugh J. Willison, Jaap J PlompAbstract:The Guillain Barre syndromes (GBS) are the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the pathophysiological events of GBS, and improving immunotherapies are fundamental to improving the clinical outcome. Recent research into GBS and the Miller Fisher syndrome (MFS) variant has focused on the forms mediated by anti-ganglioside antibodies in which correlations have been established between anti-ganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/GD1a antibodies and the acute motor axonal variant and anti-GQ1b/GT1a antibodies and MFS. Anti-ganglioside antibodies can arise through molecular mimicry with GBS-associated Campylobacter jejuni oligosaccharides. Our work has focused on axonal and glial components of the motor Nerve Terminal as a model site of injury, and through combined active and passive immunization paradigms in glycosyltransferase knockout mice we have developed murine neuropathy phenotypes mediated by anti-ganglioside antibodies. Several determinants influence disease expression including the level of immunological tolerance to microbial glycans that mimic self gangliosides, the degree of complement activation, and the ganglioside density in target tissue. Such studies provide us with clear information on an antibody-mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in man.
Elis F Stanley - One of the best experts on this subject based on the ideXlab platform.
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g protein types involved in calcium channel inhibition at a presynaptic Nerve Terminal
The Journal of Neuroscience, 2000Co-Authors: Rukmini R Mirotznik, Xu Zheng, Elis F StanleyAbstract:The inhibition of presynaptic calcium channels via G-protein-dependent second messenger pathways is a key mechanism of transmitter release modulation. We used the calyx-type Nerve Terminal of the chick ciliary ganglion to examine which G-proteins are involved in the voltage-sensitive inhibition of presynaptic N-type calcium channels. Adenosine caused a prominent inhibition of the calcium current that was totally blocked by pretreatment with pertussis toxin (PTX), consistent with an exclusive involvement of Go/Gi in the G-protein pathway. Immunocytochemistry was used to localize these G-protein types to the Nerve Terminal and its transmitter release face. We used two approaches to test for modulation by other G-protein types. First, we treated the Terminals with ligands for a variety of G-protein-linked neurotransmitter receptor types that have been associated with different G-protein families. Although small inhibitory effects were observed, these could all be eliminated by PTX, indicating that in this Terminal the Gi family is the sole transmitter-induced G-protein inhibitory pathway. Second, we examined the kinetics of calcium channel inhibition by uncaging the nonselective and irreversible G-protein activator GTPγS, bypassing the receptors. A large fraction of the rapid GTPγS-induced inhibition persisted, consistent with a Go/Gi-independent pathway. Immunocytochemistry identified Gq, G11, G12, and G13 as potential PTX-insensitive second messengers at this Terminal. Thus, our results suggest that whereas neurotransmitter-mediated calcium channel inhibition is mainly, and possibly exclusively, via Go/Gi, other rapid PTX-insensitive G-protein pathways exist that may involve novel, and perhaps transmitter-independent, activating mechanisms.
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single channel properties of bk type calcium activated potassium channels at a cholinergic presynaptic Nerve Terminal
The Journal of Physiology, 1999Co-Authors: Xiao Ping Sun, Lyanne C Schlichter, Elis F StanleyAbstract:Substantial evidence suggests that most, if not all, Nerve Terminals that secrete neurotransmitters by action potential-dependent mechanisms exhibit a calcium-activated potassium (KCa) channel. Such Terminals include presynaptic Nerve Terminals at fast-transmitting synapses (Bartschat & Blaustein, 1985; Farley & Rudy, 1988; Anderson et al. 1988; Lindgren & Moore, 1989; Schneider et al. 1989; Astrand & Stjarne, 1991; Sivaramakrishnan et al. 1991; Robitaille & Charlton, 1992; Wangemann & Takeuchi, 1993; Blundon et al. 1995; Rahamimoff et al. 1995; Katz et al. 1997; Sakaba et al. 1997; Yazejian et al. 1997), hormone-secreting Nerve Terminals (Bielefeldt et al. 1992; Wang & Lemos, 1992; Wang et al. 1992; Bielefeldt & Jackson, 1993) and sense-organ cells (such as hair cells, Edgington & Stewart, 1981; Roberts et al. 1990, 1991; Issa & Hudspeth, 1994; Art et al. 1995) which share many properties with fast-transmitting Nerve Terminals. It is not clear which specific types of KCa channel are present at most of these sites but, where tested by specific staining or direct recording, the high-conductance, BK-type has been repeatedly observed (Smith et al. 1986; Castle & Strong, 1986; Roberts et al. 1991; Robitaille & Charlton, 1992; Bielefeldt & Jackson, 1993; Wangemann & Takeuchi, 1993; Issa & Hudspeth, 1994; Art et al. 1995; Knaus et al. 1996). Other studies have presented more indirect evidence for the presence of this channel in the Nerve Terminal on the basis of effects of peptide blockers, primarily charybdotoxin (CTX) or iberiotoxin (IbTX), or intracellular buffers on transmitter release (Kumamoto & Kuba, 1985; Sivaramakrishnan et al. 1991; Robitaille & Charlton, 1992; Stretton et al. 1992; Takeuchi & Wangemann, 1993; Robitaille et al. 1993; Yazejian et al. 1997). Despite the evident broad distribution of BK channels in Nerve Terminals little is known about their biophysical properties and to what extent these may differ from their relatives in the cell soma. This question has become of particular interest recently with the discovery that the BK channel can be expressed in many functionally different isoforms (Butler et al. 1993; Wei et al. 1998). In addition, the channel can associate with a β subunit (Vergara et al. 1998) that has marked effects on its biophysical and pharmacological properties. Thus, because of this diversity a full understanding of the role of this channel in the Nerve Terminal requires direct recording of its properties in situ. Furthermore, the complex activation characteristics of the BK channel require analysis at the single-channel level since it is gated by both a ligand and a physical factor, i.e. calcium and voltage. There have been only two Nerve Terminals at which the single-channel properties of BK channels have been examined (Wang et al. 1992; Wangemann & Takeuchi, 1993; Bielefeldt & Jackson, 1993) due, presumably, to the general small size and inaccessibility of these structures. Few Nerve Terminals are of sufficiently large size to permit direct patch-clamp recording, and in the cases where this is possible obtaining sufficient data requires considerable experimental effort. This study presents the first characterization of single BK channels at the presynaptic Nerve Terminal of a neuron-to-neuron synapse. We used the calyx-type synapse of the chick ciliary ganglion (CCG) to record and characterize single presynaptic high-conductance KCa channels. This experimental preparation was the first in which an intact vertebrate presynaptic Terminal could be voltage clamped to record whole-Terminal currents (Stanley, 1989) or clamped in the cell-attached configuration (Stanley, 1991) to record single-channel activity. We have recently presented evidence for the presence of KCa channels on this Terminal by direct recording of an outwardly rectifying K+ current that was sensitive to CTX and IbTX (Tozer et al. 1998). In this study we first used the patch-clamp technique in the outside-out and inside-out configurations to test for block with standard K+ channel blockers. We next used the same techniques to examine the voltage and calcium sensitivity of single BK channels. Finally, we used the cell-attached configuration to test whether presynaptic BK channels could be activated by calcium influx through the same membrane patch.
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an atp activated ligand gated ion channel on a cholinergic presynaptic Nerve Terminal
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Xiao Ping Sun, Elis F StanleyAbstract:Abstract ATP has recently been identified as a fast neurotransmitter in both the central and peripheral nervous systems. Several studies have suggested that ATP can also affect the release of classical neurotransmitters, including acetylcholine with which it is co-released. We have searched for ATP receptors on a cholinergic presynaptic Nerve Terminal using the calyx-type synapse of the chicken ciliary ganglion. ATP was pulsed onto the Terminals under voltage clamp and induced a short latency cation current that exhibited inward rectification and marked desensitization. This current was not seen with adenosine but was mimicked by several sterically restricted ATP analogs and was blocked by suramin. ATP-activated single ion channels exhibited prominent flickering and had a conductance of approximately 17 pS. Our results demonstrate a ligand-gated P2X-like purinergic receptor on a cholinergic presynaptic Nerve Terminal.
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localization of individual calcium channels at the release face of a presynaptic Nerve Terminal
Neuron, 1994Co-Authors: Eric Henderson, Elis F StanleyAbstract:Summary Studies using biophysical techniques suggest a highly structured organization of calcium channels at the presynaptic transmitter release face (Llinas et al., 1981; Stanley, 1993), but it has not as yet proved possible to localize identified channels at the required nanometer level of resolution. We have used atomic force microscopy on the calyx-type Nerve Terminal of the chick ciliary ganglion to localize single calcium channels tagged via biotinylated ω-conotoxin GVIA to avidin-coated 30 nm gold particles. Calcium channels were in low (modal value approximately ⩽ 1 per μm 2 ) and high (modal value55 per μm 2 ) density areas and exhibited a prominent interchannel spacing of 40 nm, indicating an intermolecular linkage. Particles were observed in clusters and short linear or parallel linear arrays, groupings that may reflect calcium channel organization at the transmitter release site.
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single calcium channels on a cholinergic presynaptic Nerve Terminal
Neuron, 1991Co-Authors: Elis F StanleyAbstract:Abstract The calyx-type synapse of the chick ciliary ganglion was used to examine single calcium channels in a vertebrate cholinergic presynaptic Nerve Terminal by means of the cell-attached, patch-clamp technique. Calcium channels were recorded on the internal, transmitter-release face of the Nerve Terminal, but were not detected on the external face. These channels were recruited at −30 mV, with maximum activation at about +30 mV, and were sometimes clustered at high densities. Single-channel conductance estimates with voltage-pulse or-ramp techniques gave values of 11–14 pS with 110 mM barium, which is in the intermediate, N-type range for calcium channels on a control neuron. This Nerve Terminal calcium channel, termed the N PT -type, may link action potentials to transmitter release at many vertebrate fast-transmitting synapses.
Graham M. O'hanlon - One of the best experts on this subject based on the ideXlab platform.
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Calpain inhibitors protect against axonal degeneration in a model of anti-ganglioside antibody-mediated motor Nerve Terminal injury.
Brain, 2003Co-Authors: Graham M. O'hanlon, Susan K Halstead, Peter D Humphreys, Jaap J Plomp, Rebecca S Goldman, Roland W M Bullens, Yuri Ushkaryov, Hugh J. WillisonAbstract:Summary Miller Fisher syndrome-associated anti-GQ1b ganglioside antibodies produce an acute complement-dependent neuroexocytic effect at the mouse neuromuscular junction (NMJ) that closely resembles the effect of a-latrotoxin (LTx). This pathophysiological effect is accompanied by morphological disruption of the Nerve Terminal involving the loss of major cytoskeletal components, including neurofilament. Both LTx and the membrane attack complex of complement form membrane pores that allow free ionic movement and we have previously hypothesized that Ca 2+ ingress and the subsequent activation of Ca 2+ -dependent proteases, cal
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Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor Nerve Terminal
Brain, 2001Co-Authors: Graham M. O'hanlon, Eric R Wagner, Jaap J Plomp, Mahua Chakrabarti, Ian Morrison, Carl S. Goodyear, Xinghua Yin, Bruce D. Trapp, Joe Conner, Peter C. M. MolenaarAbstract:Miller–Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent α-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III β-tubulin immunostaining and structural breakdown of the Nerve Terminal, as demonstrated by electron microscopy. Ultrastructurally, axon Terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating Nerve Terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.
David L Hill - One of the best experts on this subject based on the ideXlab platform.
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impact of chorda tympani Nerve injury on cell survival axon maintenance and morphology of the chorda tympani Nerve Terminal field in the nucleus of the solitary tract
The Journal of Comparative Neurology, 2012Co-Authors: Rebecca Reddaway, Andrew W Davidow, Sarah L Deal, David L HillAbstract:Chorda tympani Nerve transection (CTX) has been useful to study the relationship between Nerve and taste buds in fungiform papillae. This work demonstrated that the morphological integrity of taste buds depends on their innervation. Considerable research focused on the effects of CTX on peripheral gustatory structures, but much less research has focused on the central effects. Here, we explored how CTX affects ganglion cell survival, maintenance of injured peripheral axons, and the chorda tympani Nerve Terminal field organization in the nucleus of the solitary tract (NTS). After CTX in adult rats, the chorda tympani Nerve was labeled with biotinylated dextran amine at 3, 7, 14, 30, and 60 days post-CTX to allow visualization of the Terminal field associated with peripheral processes. There was a significant and persistent reduction of the labeled chorda tympani Nerve Terminal field volume and density in the NTS following CTX. Compared with controls, the volume of the labeled Terminal field was not altered at 3 or 7 days post-CTX; however, it was significantly reduced by 44% and by 63% at 30 and 60 days post-CTX, respectively. Changes in the density of labeled Terminal field in the NTS paralleled the Terminal field volume results. The dramatic decrease in labeled Terminal field size post-CTX cannot be explained by a loss of geniculate ganglion neurons or degeneration of central axons. Instead, the function and/or maintenance of the peripheral axonal process appear to be affected. These new results have implications for long-term functional and behavioral alterations.
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chorda tympani Nerve Terminal field maturation and maintenance is severely altered following changes to gustatory Nerve input to the nucleus of the solitary tract
The Journal of Neuroscience, 2011Co-Authors: Stephen L. Corson, David L HillAbstract:Neural competition among multiple inputs can affect the refinement and maintenance of Terminal fields in sensory systems. In the rat gustatory system, the chorda tympani, greater superficial petrosal, and glossopharyngeal Nerves have distinct but overlapping Terminal fields in the first central relay, the nucleus of the solitary tract. This overlap is largest at early postnatal ages followed by a significant refinement and pruning of the fields over a 3 week period, suggesting that competitive mechanisms underlie the pruning. Here, we manipulated the putative competitive interactions among the three Nerves by sectioning the greater superficial petrosal and glossopharyngeal Nerves at postnatal day 15 (P15), P25, or at adulthood, while leaving the chorda tympani Nerve intact. The Terminal field of the chorda tympani Nerve was assessed 35 d following Nerve sections, a period before the sectioned Nerves functionally regenerated. Regardless of the age when the Nerves were cut, the chorda tympani Nerve Terminal field expanded to a volume four times larger than sham controls. Terminal field density measurements revealed that the expanded Terminal field was similar to P15 control rats. Thus, it appears that the chorda tympani Nerve Terminal field defaults to its early postnatal field size and shape when the Nerves with overlapping fields are cut, and this anatomical plasticity is retained into adulthood. These findings not only demonstrate the dramatic and lifelong plasticity in the central gustatory system, but also suggest that corresponding changes in functional and taste-related behaviors will accompany injury-induced changes in brainstem circuits.