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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.
|Number of pages||16|
|Early online date||29 Jan 2015|
|Publication status||Published - Jun 2015|
- leukemia inhibitory factor
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- 1 Finished
THE ROLE OF GALANIN IN THE ADAPTIVE RESPONSE OF THE PERIPHERAL NERVOUS SYSTEMT O INJURY
1/08/03 → 1/08/08
Professor David Wynick
- Bristol Medical School (THS) - Professor of Molecular Medicine
- Elizabeth Blackwell Institute for Health Research
- Bristol Neuroscience
Person: Academic , Member