title: Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.
abstract: Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC-rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU-positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate-mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α-cyano-4-hydroxy-cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986-995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
authors.affiliation: Department of Rehabilitation for Movement Functions, National Rehabilitation Center for Persons With Disabilities, Saitama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ichihara
authors.affiliation: Department of Rehabilitation for Movement Functions, National Rehabilitation Center for Persons With Disabilities, Saitama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Rehabilitation for Movement Functions, National Rehabilitation Center for Persons With Disabilities, Saitama, Japan.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Department of Rehabilitation for Movement Functions, National Rehabilitation Center for Persons With Disabilities, Saitama, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Rehabilitation for Movement Functions, National Rehabilitation Center for Persons With Disabilities, Saitama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Department of Rehabilitation for Movement Functions, National Rehabilitation Center for Persons With Disabilities, Saitama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000818:Animals; D001089:Arabinose / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D050113:Imino Furanoses / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013402:Sugar Alcohols / Q000494:pharmacology
chemical_list: D050113:Imino Furanoses; D027501:Monocarboxylic Acid Transporters; D013402:Sugar Alcohols; C058137:1,4-dideoxy-1,4-iminoarabinitol; D019344:Lactic Acid; D003471:Cuprizone; D001089:Arabinose; D005947:Glucose