title: Alterations of juxtaparanodal domains in two rodent models of CNS demyelination.
abstract: The segregation of myelinated fibers into distinct domains around the node of Ranvier--the perinodal areas--is crucial for nervous system homeostasis and efficient nerve conduction. Perinodal areas are formed by axo-glial interactions, namely the interaction of molecules between the axon and the myelinating glia. In a variety of demyelinating pathologies including multiple sclerosis, the molecular architecture of the myelinated fiber is disrupted, leading to axonal degeneration. In this study we have analyzed the alterations of TAG-1, Caspr2, and voltage-gated potassium channels (VGKCs), forming the juxtaparanodal tripartite complex, in relation to adjacent paranodal and nodal molecules, in two different models of CNS demyelination, the experimental autoimmune encephalomyelitis (EAE) and the cuprizone model of toxic demyelination. We found extensive alterations of the juxtaparanodal molecular architecture under de- and remyelinating conditions. Inflammation alone was sufficient to disrupt the borders between the domains leading to the diffusion of juxtaparanodal components to the adjacent paranodal area. EAE induction and cuprizone-induced demyelination resulted initially in paranodal domain elongation with subsequent diffusion of the juxtaparanodal components and the reduction of their expression levels. At later stages, with decreasing inflammation and spontaneous remyelination there was a partial restoration of the paranodal domain but not sufficient re-organization of the juxtaparanodes. The latter were re-formed only when complete remyelination was allowed in the cuprizone model, indicating that juxtaparanodal domain reorganization is a later event that may remain incomplete in a hostile inflammatory milieu.
authors.affiliation: Department of Basic Science, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Lida
authors.initials: L
authors.lastname: Zoupi
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Markoullis
authors.forename: Kleopas A
authors.initials: KA
authors.lastname: Kleopa
authors.forename: Domna
authors.initials: D
authors.lastname: Karagogeos
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017434:Protein Structure, Tertiary
chemical_list: D003471:Cuprizone
keywords: EAE; cuprizone; demyelination; nodes of Ranvier; paranodes