Cuprizone demyelination induces a unique inflammatory response in the subventricular zone

Cuprizone demyelination induces a unique inflammatory response in the subventricular zone

Author Hillis, James M. Google Scholar
Davies, Julie Google Scholar
Mundim, Mayara Vieira Autor UNIFESP Google Scholar
Al-Dalahmah, Osama Google Scholar
Szele, Francis G. Google Scholar
Abstract Background: Cuprizone leads to demyelination of the corpus callosum (CC) and activates progenitor cells in the adjacent subventricular zone (SVZ), a stem cell niche which contributes to remyelination. The healthy SVZ contains semi-activated microglia and constitutively expresses the pro-inflammatory molecule galectin-3 (Gal-3) suggesting the niche uniquely regulates inflammation. Methods: We studied the inflammatory response to cuprizone in the SVZ and CC in Gal-3 knockout mice using immunohistochemistry and with the in vitro neurosphere assay. Results: Cuprizone caused loss of myelin basic protein (MBP) immunofluorescence in the CC suggesting demyelination. Cuprizone increased the density of CD45+/Iba1+ microglial cells and also increased Gal-3 expression in the CC. Surprisingly, the number of Gal-3+ and CD45+ cells decreased in the SVZ after cuprizone, suggesting inflammation was selectively reduced therein. Inflammation can regulate SVZ proliferation and indeed the number of phosphohistone H3+ (PHi3+) cells decreased in the SVZ but increased in the CC in both genotypes after cuprizone treatment. BrdU+ SVZ cell numbers also decreased in the SVZ after cuprizone, and this effect was significantly greater at 3 weeks in Gal-3(-/-) mice compared to WT, suggesting Gal-3 normally limits SVZ cell emigration following cuprizone treatment. Conclusions: This study reveals a uniquely regulated inflammatory response in the SVZ and shows that Gal-3 participates in remyelination in the cuprizone model. This contrasts with more severe models of demyelination which induce SVZ inflammation and suggests the extent of demyelination affects the SVZ neurogenic response.
Keywords Subventricular zone
Multiple sclerosis
Corpus callosum
Language English
Sponsor University of Oxford Clarendon Scholarship
Oxford-Australia Scholarship
Date 2016
Published in Journal Of Neuroinflammation. London, v. 13, p. -, 2016.
ISSN 1742-2094 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent -
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000382837000002

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