title: Block of a subset of sodium channels exacerbates experimental autoimmune encephalomyelitis.
abstract: Voltage-gated sodium channels (Navs) 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 Nav blockers. Further, block of specific Navs 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 Nav1.2, Nav1.4 and Nav1.6. Administration of this Midi peptide worsens the clinical disease pattern and Nav1.2 and Nav1.6 expression levels were elevated in brain but not in spinal cord of Midi-treated mice, implicating that Navs play a complex role in the pathogenesis of EAE.
authors.affiliation: Laboratory of Toxicology, Department of Pharmaceutical Sciences, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49 Box 922, B-3000 Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Stevens
authors.forename: Silke
authors.initials: S
authors.lastname: Timmermans
authors.forename: Astrid
authors.initials: A
authors.lastname: Bottelbergs
authors.forename: Jerome J A
authors.initials: JJ
authors.lastname: Hendriks
authors.forename: Bert
authors.initials: B
authors.lastname: Brône
authors.forename: Myriam
authors.initials: M
authors.lastname: Baes
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D060326:Chemistry Techniques, Synthetic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000096:biosynthesis / Q000378:metabolism*; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000096:biosynthesis / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000633:toxicity; D026941:Sodium Channel Blockers / Q000633:toxicity*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D010446:Peptide Fragments; C491046:Scn8a protein, mouse; D026941:Sodium Channel Blockers; D015222:Sodium Channels
keywords: EAE; Experimental autoimmune encephalomyelitis; MOG; MS; Macrophages; Microglia; Multiple sclerosis; Na(v); Neuroprotection; PBS; PHT; TTX; Voltage-gated sodium channel; experimental autoimmune encephalomyelitis; multiple sclerosis; myelin oligodendrocyte glycoprotein; phenytoin; phosphate buffered saline; tetrodotoxin; voltage-gated sodium channel