Cuprizone demyelination induces a unique inflammatory response in the subventricular zone

Show simple item record Hillis, James M. Davies, Julie Mundim, Mayara Vieira [UNIFESP] Al-Dalahmah, Osama Szele, Francis G. 2019-07-22T15:46:54Z 2019-07-22T15:46:54Z 2016
dc.identifier.citation Journal Of Neuroinflammation. London, v. 13, p. -, 2016.
dc.identifier.issn 1742-2094
dc.description.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. en
dc.description.sponsorship University of Oxford Clarendon Scholarship
dc.description.sponsorship Oxford-Australia Scholarship
dc.format.extent -
dc.language.iso eng
dc.publisher Biomed Central Ltd
dc.rights Acesso aberto
dc.subject Subventricular zone en
dc.subject Multiple sclerosis en
dc.subject Inflammation en
dc.subject Galectin-3 en
dc.subject Corpus callosum en
dc.subject Demyelination en
dc.title Cuprizone demyelination induces a unique inflammatory response in the subventricular zone en
dc.type Artigo
dc.description.affiliation Univ Oxford, Dept Physiol Anat & Genet, South Parks Rd, Oxford OX1 3QX, England
dc.description.affiliation Univ Fed Sao Paulo, Dept Biochem, BR-04039032 Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Biochem, BR-04039032 Sao Paulo, Brazil
dc.identifier.file WOS000382837000002.pdf
dc.identifier.doi 10.1186/s12974-016-0651-2
dc.description.source Web of Science
dc.identifier.wos WOS:000382837000002


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