Block of a subset of sodium channels exacerbates experimental autoimmune encephalomyelitis

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• 作者：Marijke Stevens ; Silke Timmermans ; Astrid Bottelbergs ; Jerome J.A. Hendriks ; Bert Br?ne ; Myriam Baes ; Jan Tytgat
• 关键词：EAE ; experimental autoimmune encephalomyelitis ; MOG ; myelin oligodendrocyte glycoprotein ; MS ; multiple sclerosis ; Nav ; voltage-gated sodium channel ; PBS ; phosphate buffered saline ; PHT ; phenytoin ; TTX ; tetrodotoxin
• 刊名：Journal of Neuroimmunology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：261
• 期：1-2
• 页码：21-28
• 全文大小：680 K

文摘

Voltage-gated sodium channels (Na_vs) are involved in several aspects of the pathogenesis of multiple sclerosis (MS). Within acute MS plaques, they are expressed along demyelinated axons. Studies in experimental autoimmune encephalomyelitis (EAE) demonstrated a neuroprotective effect of non-specific Na_v blockers. Further, block of specific Na_vs involved in MS is suggested to have an advantage over non-specific blockers. We investigated the effects of the synthetic Midi peptide in EAE, as it potently and specifically blocks Na_v1.2, Na_v1.4 and Na_v1.6. Administration of this Midi peptide worsens the clinical disease pattern and Na_v1.2 and Na_v1.6 expression levels were elevated in brain but not in spinal cord of Midi-treated mice, implicating that Na_vs play a complex role in the pathogenesis of EAE.