title: Leptin sustains spontaneous remyelination in the adult central nervous system.
abstract: Demyelination is a common feature of many central nervous system (CNS) diseases and is associated with neurological impairment. Demyelinated axons are spontaneously remyelinated depending on oligodendrocyte development, which mainly involves molecules expressed in the CNS environment. In this study, we found that leptin, a peripheral hormone secreted from adipocytes, promoted the proliferation of oligodendrocyte precursor cells (OPCs). Leptin increased the OPC proliferation via in vitro phosphorylation of extracellular signal regulated kinase (ERK); whereas leptin neutralization inhibited OPC proliferation and remyelination in a mouse model of toxin-induced demyelination. The OPC-specific leptin receptor long isoform (LepRb) deletion in mice inhibited both OPC proliferation and remyelination in the response to demyelination. Intrathecal leptin administration increased OPC proliferation. These results demonstrated a novel molecular mechanism by which leptin sustained OPC proliferation and remyelination in a pathological CNS.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Matoba
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.|Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Muramatsu
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000502:physiology*; D005260:Female; D020738:Leptin / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D000074586:Remyelination / Q000502:physiology*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin