Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor

• Published in: Glia Vol. 63; no. 6; pp. 1005 - 1020
• Main Authors: Gresle, Melissa M., Butzkueven, Helmut, Perreau, Victoria M., Jonas, Anna, Xiao, Junhua, Thiem, Stefan, Holmes, Fiona E., Doherty, William, Soo, Pik-Ying, Binder, Michele D., Akkermann, Rainer, Jokubaitis, Vilija G., Cate, Holly S., Marriott, Mark P., Gundlach, Andrew L., Wynick, David, Kilpatrick, Trevor J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.06.2015; Wiley Subscription Services, Inc
• Subjects: Animals; Astrocytes - pathology; Astrocytes - physiology; Brain - pathology; Brain - physiopathology; Cell Survival - physiology; Cells, Cultured; Cuprizone; Demyelinating Diseases - pathology; Demyelinating Diseases - physiopathology; Disease Models, Animal; galanin; Galanin - genetics; Galanin - metabolism; Gene Expression; Leukemia; leukemia inhibitory factor; Leukemia Inhibitory Factor - metabolism; MAP Kinase Signaling System - physiology; Medical research; Mice, Inbred C57BL; Mice, Knockout; Myelin Sheath - pathology; Myelin Sheath - physiology; Neural Stem Cells - pathology; Neural Stem Cells - physiology; oligodendrocytes; Oligodendroglia - pathology; Oligodendroglia - physiology; Optic Nerve - pathology; Optic Nerve - physiology; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Rodents; leukemia inhibitory factor; oligodendrocytes; galanin
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.22798

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. GLIA 2015;63:1005–1020 Main Points Three known trophic factors for oligodendrocytes (LIF, NT3, Insulin) induce largely non‐overlapping gene expression changes in post‐mitotic oligodendrocytes (OC). LIF induces the synthesis and secretion of galanin in OC in vivo and in vitro. LIF‐induced OC survival is mediated via auto/paracrine galanin secretion.