Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 15, Pages 3956-3967Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4401-06.2007
Keywords
Guillain-Barre syndrome; node of Ranvier; sodium channel; ganglioside; autoantibodies; complement
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Funding
- NINDS NIH HHS [R01 NS044916, R37 NS044916, NS044916] Funding Source: Medline
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Voltage-gated Na+ (Na-v) channels are highly concentrated at nodes of Ranvier in myelinated axons and facilitate rapid action potential conduction. Autoantibodies to gangliosides such as GM1 have been proposed to disrupt nodal Nav channels and lead to Guillain-Barre syndrome, an autoimmune neuropathy characterized by acute limb weakness. To test this hypothesis, we examined the molecular organization of nodes in a disease model caused by immunization with gangliosides. At the acute phase with progressing limb weakness, Nav channel clusters were disrupted or disappeared at abnormally lengthened nodes concomitant with deposition of IgG and complement products. Paranodal axoglial junctions, the nodal cytoskeleton, and Schwann cell microvilli, all of which stabilize Na-v channel clusters, were also disrupted. The nodal molecules disappeared in lesions with complement deposition but no localization of macrophages. During recovery, complement deposition at nodes decreased, and Nav channels redistributed on both sides of affected nodes. These results suggest that Na-v channel alterations occur as a consequence of complement-mediated disruption of interactions between axons and Schwann cells. Our findings support the idea that acute motor axonal neuropathy is a disease that specifically disrupts the nodes of Ranvier.
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