title: Remyelination after cuprizone induced demyelination is accelerated in mice deficient in the polysialic acid synthesizing enzyme St8siaIV.
abstract: Polysialic acid (PSA) is a carbohydrate polymer added post-translationally on the neural cell adhesion molecule (NCAM) affecting its adhesion properties. It has been suggested that the presence of PSA in demyelinated lesions in multiple sclerosis could prevent axon-glia interactions inhibiting spontaneous remyelination. The enzyme St8siaIV is one of the two polysialyltransferases responsible for PSA synthesis, and it is predominantly active during adult life. Here we treated 8-10-weeks old St8siaIV deficient and wild-type mice for 5 weeks with cuprizone, which is a reliable model for de- and remyelination in the corpus callosum and cortex. Developmental myelination of the St8siaIV knock-out mice was not disturbed and adult mice showed normal myelin protein expression. Demyelination did not differ between transgenic and wild-type mice but early myelin protein re-expression and thus remyelination were accelerated in St8siaIV knock-out mice during the first week after withdrawal of the toxin. This was mainly due to enhanced oligodendrocyte precursor cells (OPC) differentiation and to a lesser extent to OPC recruitment. These data are proof of principle that PSA expression interferes at least to some extent with remyelination in vivo.
authors.affiliation: Department of Neurology, Hannover Medical School, Carl-Neuberg-Street-1, 30625 Hanover, Germany.
authors.forename: P N
authors.initials: PN
authors.lastname: Koutsoudaki
authors.forename: H
authors.initials: H
authors.lastname: Hildebrandt
authors.forename: V
authors.initials: V
authors.lastname: Gudi
authors.forename: T
authors.initials: T
authors.lastname: Skripuletz
authors.forename: J
authors.initials: J
authors.lastname: Škuljec
authors.forename: M
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000070798:Nogo Proteins; D011509:Proteoglycans / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D012794:Sialic Acids / Q000378:metabolism; D012799:Sialyltransferases / Q000172:deficiency*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D000943:Antigens, Differentiation; D003471:Cuprizone; D005904:Glial Fibrillary Acidic Protein; D008996:Monoamine Oxidase Inhibitors; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D019006:Neural Cell Adhesion Molecules; D000070798:Nogo Proteins; D011509:Proteoglycans; D012794:Sialic Acids; D012799:Sialyltransferases; D000099216:Chondroitin Sulfate Proteoglycan 4; C571327:Mog protein, mouse; C047516:Plp1 protein, mouse; C000603201:Rtn4 protein, mouse; C036763:monocyte-macrophage differentiation antigen; C021319:polysialic acid