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

Melissa M Gresle, Helmut Butzkueven, Victoria M Perreau, Anna Jonas, Junhua Xiao, Stefan Thiem, Fiona E Holmes, William Doherty, Pik-Ying Soo, Michele D Binder, Rainer Akkermann, Vilija G Jokubaitis, Holly S Cate, Mark P Marriott, Andrew L Gundlach, David Wynick, Trevor J Kilpatrick

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.

Original languageEnglish
Pages (from-to)1005-1020
Number of pages16
JournalGlia
Volume63
Issue number6
Early online date29 Jan 2015
DOIs
Publication statusPublished - Jun 2015

Keywords

  • leukemia inhibitory factor
  • galanin
  • oligodendrocytes

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