title: [Demyelination and oligodendrocytes].
abstract: Although neurological sequelae are attributable to poor regeneration of the central nervous system, oligodendrocytes demonstrate robust regenerative response even in adults. Accumulating evidence indicates that the glial cells identified by surface expression of the proteoglycan NG2 are the cellular source of newly-developed oligodendrocytes following demyelination, and thereby considered adult oligodendroglial progenitor cells (OPCs). Despite their robust regenerative capability, remyelination often ends up in failure or is incomplete, particularly after recurrent neuroinflammation, which is referred to as "remyelination failure". While axonal degeneration may contribute to remyelination failure, OPCs are also affected by neuroinflammation. Indeed, various studies have indicated that gamma-interferon, a proinflammatory cytokine associated with autoimmunity, is cytotoxic to OPCs by inducing cell death, and inhibiting their proliferation and differentiation. In contrast to gamma-interferon, we confirmed that beta-interferon which is used for the treatment of relapsing-remitting multiple sclerosis does not induce OPC death. Through a comprehensive analysis of gamma-interferon-inducible and beta-interferon-inducible genes in OPCs, we have identified interferon regulatory factor-1 and -8 (IRF1 and IRF8) as candidate transcription factors responsible for gamma-interferon-mediated cytotoxicity in OPCs. Validating and elaborating on these findings particularly in in vivo models may prove of importance in understanding remyelination failure and suggest therapeutic approaches to enhance remyelination.
authors.affiliation: Department of Neurology/Shriners Hospitals for Children Northern California, University of California Davis, School of Medicine, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Itoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Kouji
authors.initials: K
authors.lastname: Wakayama
authors.forename: Aki
authors.initials: A
authors.lastname: Itoh
authors.forename: David
authors.initials: D
authors.lastname: Pleasure
mesh_terms: D000818:Animals; D002417:Cattle; D016923:Cell Death; D003711:Demyelinating Diseases / Q000503:physiopathology*; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D009836:Oligodendroglia / Q000502:physiology*
chemical_list: D007371:Interferon-gamma