title: Minocycline reduces remyelination by suppressing ciliary neurotrophic factor expression after cuprizone-induced demyelination.
abstract: Remyelination is disrupted in demyelinating diseases such as multiple sclerosis, but the underlying pathogenetic mechanisms are unclear. In this study, we employed the murine cuprizone model of demyelination, in which remyelination occurs after removal of the toxin from the diet, to examine the cellular and molecular changes during demyelination and remyelination. Microglia accumulated in the corpus callosum during weeks 2-4 of the cuprizone diet, and these cells remained activated 2 weeks after the change to the normal diet. To examine the role of microglia in remyelination, mice were treated with minocycline to inactivate these cells after cuprizone-induced demyelination. Minocycline treatment reduced the number of CC1-positive oligodendrocytes, as well as levels of myelin basic protein (MBP) and CNPase in the remyelination phase. The expression of CNTF mRNA in the corpus callosum increased after 4 weeks on the cuprizone diet and remained high 2 weeks after the change to the normal diet. Minocycline suppressed CNTF expression during the remyelination phase on the normal diet. Primary culture experiments showed that CNTF was produced by microglia in addition to astrocytes. In vitro, CNTF directly affected the differentiation of oligodendrocytic cells. These findings suggest that minocycline reduces remyelination by suppressing CNTF expression by microglia after cuprizone-induced demyelination.
authors: Department of Functional Anatomy and Neuroscience, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors: Tatsuhide
authors: T
authors: Tanaka
authors: Koichi
authors: K
authors: Murakami
authors: Yoshio
authors: Y
authors: Bando
authors: Shigetaka
authors: S
authors: Yoshida
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D020934:Ciliary Neurotrophic Factor; D008996:Monoamine Oxidase Inhibitors; D004676:Myelin Basic Protein; D003471:Cuprizone; D008911:Minocycline
keywords: CNTF; cuprizone; demyelination; microglia; minocycline; remyelination