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- Title
Cuprizone demyelination induces a unique inflammatory response in the subventricular zone.
- Authors
Hillis, James M.; Davies, Julie; Mundim, Mayara Vieira; Al-Dalahmah, Osama; Szele, Francis G.
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
DEMYELINATION; LECTINS; CORPUS callosum; INFLAMMATION; PROGENITOR cells; IMMUNOCYTOCHEMISTRY; LABORATORY mice; DISEASES; THERAPEUTICS; ANIMAL experimentation; ANIMAL populations; ANIMALS; BIOLOGICAL models; CEREBRAL ventricles; CALCIUM-binding proteins; CELL physiology; CENTRAL nervous system; CYTOSKELETAL proteins; GENES; HYDROCARBONS; MICE; MICROFILAMENT proteins; MONOAMINE oxidase inhibitors; PROTEINS; TELENCEPHALON; NEURAL pathways; DISEASE complications
- Publication
Journal of Neuroinflammation, 2016, Vol 13, p1
- ISSN
1742-2094
- Publication type
journal article
- DOI
10.1186/s12974-016-0651-2