title: Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor.
abstract: In order to further investigate the molecular mechanisms that regulate oligodendrocyte (OC) survival, we utilized microarrays to characterize changes in OC gene expression after exposure to the cytokines neurotrophin3, insulin, or leukemia inhibitory factor (LIF) in vitro. We identified and validated the induction and secretion of the neuropeptide galanin in OCs, specifically in response to LIF. We next established that galanin is an OC survival factor and showed that autocrine or paracrine galanin secretion mediates LIF-induced OC survival in vitro. We also revealed that galanin is up-regulated in OCs in the cuprizone model of central demyelination, and that oligodendroglial galanin expression is significantly regulated by endogenous LIF in this context. We also showed that knock-out of galanin reduces OC survival and exacerbates callosal demyelination in the cuprizone model. These findings suggest a potential role for the use of galanin agonists in the treatment of human demyelinating diseases.
authors: Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Australia; Department of Medicine, University of Melbourne, Australia.
authors: Melissa M
authors: MM
authors: Gresle
authors: Helmut
authors: H
authors: Butzkueven
authors: Victoria M
authors: VM
authors: Perreau
authors: Anna
authors: A
authors: Jonas
authors: Junhua
authors: J
authors: Xiao
authors: Stefan
authors: S
authors: Thiem
authors: Fiona E
authors: FE
authors: Holmes
authors: William
authors: W
authors: Doherty
authors: Pik-Ying
authors: PY
authors: Soo
authors: Michele D
authors: MD
authors: Binder
authors: Rainer
authors: R
authors: Akkermann
authors: Vilija G
authors: VG
authors: Jokubaitis
authors: Holly S
authors: HS
authors: Cate
authors: Mark P
authors: MP
authors: Marriott
authors: Andrew L
authors: AL
authors: Gundlach
authors: David
authors: D
authors: Wynick
authors: Trevor J
authors: TJ
authors: Kilpatrick
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D019004:Galanin / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology*; D058953:Neural Stem Cells / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology*; D009900:Optic Nerve / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; D003471:Cuprizone; D019004:Galanin
keywords: galanin; leukemia inhibitory factor; oligodendrocytes