The neuromuscular junction of the mouse after black widow spider venom.

Duchen, L. W.; Gomez, Shawn M.; Queiroz, Lorena Lauren Chaves

doi:10.1113/jphysiol.1981.sp013787

Cited by 41 publications

(29 citation statements)

References 27 publications

(26 reference statements)

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“…Morphological analy-sis of NMJs exposed to CGM3 reveals extensive deposits of anti-disialosyl antibody and complement products, localized to both the nerve terminal and the overlying perisynaptic Schwann cells (pSCs) Halstead et al, 2004). At physiological extracellular calcium concentrations, there is a severe loss of cytoskeletal proteins that can be attenuated by calpain inhibition (O'Hanlon et al, 2003), accompanied by major physical disruption of the terminal axon, including vesicle depletion and complete separation of the axon from the postsynaptic membrane, i.e., denervation (Duchen et al, 1981;Willison and O'Hanlon, 1999;O'Hanlon et al, 2001). Using nuclear ethidium homodimer (EthD-1) uptake as an index of disrupted plasma membrane permeability (by MAC pores) and cell death (Reddy et al, 2003;Halstead et al, 2004), we have also observed concurrent pSC death at a high proportion of NMJs (Halstead et al, 2004).…”

Section: Introductionmentioning

confidence: 98%

Anti‐disialosyl antibodies mediate selective neuronal or Schwann cell injury at mouse neuromuscular junctions

Halstead

Morrison

O’Hanlon

et al. 2005

Glia

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The human paralytic neuropathy, Miller Fisher syndrome (MFS) is associated with autoantibodies specific for disialosyl epitopes on gangliosides GQ1b, GT1a, and GD3. Since these gangliosides are enriched in synaptic membranes, anti-ganglioside antibodies may target neuromuscular junctions (NMJs), thereby contributing to disease symptoms. We have shown previously that at murine NMJs, anti-disialosyl antibodies induce an alpha-latrotoxin-like effect, electrophysiologically characterized by transient massive increase of spontaneous neurotransmitter release followed by block of evoked release, resulting in paralysis of the muscle preparation. Morphologically, motor nerve terminal damage, as well as perisynaptic Schwann cell (pSC) death is observed. The relative contributions of neuronal and pSC injury to the paralytic effect and subsequent repair are unknown. In this study, we have examined the ability of subsets of anti-disialosyl antibodies to discriminate between the neuronal and glial elements of the NMJ and thereby induce either neuronal injury or pSC death. Most antibodies reactive with GD3 induced pSC death, whereas antibody reactivity with GT1a correlated with the extent of nerve terminal injury. Motor nerve terminal injury resulted in massive uncontrolled exocytosis with paralysis. However, pSC ablation induced no acute (within 1 h) electrophysiological or morphological changes to the underlying nerve terminal. These data suggest that at mammalian NMJs, acute pSC injury or ablation has no major deleterious influence on synapse function. Our studies provide evidence for highly selective targeting of mammalian NMJ membranes, based on ganglioside composition, that can be exploited for examining axonal-glial interactions both in disease states and in normal NMJ homeostasis.

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Section: Introductionmentioning

confidence: 98%

Anti‐disialosyl antibodies mediate selective neuronal or Schwann cell injury at mouse neuromuscular junctions

Halstead

Morrison

O’Hanlon

et al. 2005

Glia

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“…Such paralysis is completely reversible, and within a month or so, patients, supported by mechanical ventilation, recover completely (1)(2)(3). Paralysis in mice/rodents has a shorter duration, and again recovery is complete (4,5). Major presynaptic toxins of these venoms are α-latrotoxin (α-Ltx), taipoxin (Tpx), and β-bungarotoxin (β-Btx), respectively (6,7).…”

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confidence: 99%

“…Indeed, these neurotoxins cause activation of the calcium-activated calpains that contribute to cytoskeleton fragmentation (22). Although clearly documented (4,5,20), the regeneration of the motor axon terminals after presynaptic neurotoxins injection is poorly known in its cellular and molecular aspects. Available evidence indicates that, in general, regeneration of mechanically damaged motor neuron terminals relies on all three cellular components of the neuromuscular junction (NMJ): the neuron, the perisynaptic Schwann cells (PSCs), and the muscle cells (23,24).…”

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confidence: 99%

Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells

Duregotti

Negro

Scorzeto

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

104

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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.motor axon degeneration | presynaptic neurotoxins | mitochondrial alarmins | Schwann cells

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“…An increase in nodal axoplasmic volume might be expected to result from the influx of sodium ions and the consequent rise in intra-axonal osmotic pressure (Hill, 1950). The osmotic gradient would be markedly increased by agents such as Leiurus venom, which may prolong the duration of sodium influx (and hence of depolarization) for many seconds (Adam, Schmidt, Stiimpfli & Weiss, 1966 (Duchen, Gomez & Queiroz, 1981;Queiroz & Duchen, 1982). Unlike these, Phoneutria venom does not lead to widespread degeneration of intrafusal and extrafusal nerve terminals.…”

Section: Discussionmentioning

confidence: 99%

Effects of Phoneutria Nigriventer Spider Venom on Mouse Peripheral Nerve

et al. 1985

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SUMMARYA physiological and morphological study has been made ofthe effects of the venom of the spider Phoneutria nigriventer on peripheral nerve and skeletal muscle of the mouse. Venom was injected either into the sciatic nerve, via a glass micropipette, or into the calf muscles. Repetitive firing of nerve fibres commenced within seconds ofinjection and caused fasciculation ofmuscles and irregular trains of end-plate potentials. These physiological disturbances were associated with swelling of the nodal and paranodal axoplasm and the development of vacuoles in the periaxonal space. The segments of internode between the vacuoles became attenuated, with an increase in the density of axoplasmic organelles and a reduction in axonal calibre. The repetitive firing ceased after 1-3 h with development of conduction block. Both the physiological and the morphological abnormalities gradually resolved and by 24 h nerve conduction and morphology had largely returned to normal. It seems likely that these short-lived abnormalities are a consequence of the influx of sodium ions at the nodes of Ranvier, caused by the action of the venom on sodium channels.

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The neuromuscular junction of the mouse after black widow spider venom.

Abstract: 6. These findings show that the re-innervation oforiginal end-plates is ofimportance in facilitating the rapid return oftransmission to normal levels and limiting the extent of axonal growth.

Cited by 41 publications

References 27 publications

Anti‐disialosyl antibodies mediate selective neuronal or Schwann cell injury at mouse neuromuscular junctions

Anti‐disialosyl antibodies mediate selective neuronal or Schwann cell injury at mouse neuromuscular junctions

Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells

Effects of Phoneutria Nigriventer Spider Venom on Mouse Peripheral Nerve

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