| First Author | Hillis JM | Year | 2016 |
| Journal | J Neuroinflammation | Volume | 13 |
| Issue | 1 | Pages | 190 |
| PubMed ID | 27550173 | Mgi Jnum | J:277251 |
| Mgi Id | MGI:6330814 | Doi | 10.1186/s12974-016-0651-2 |
| Citation | Hillis JM, et al. (2016) Cuprizone demyelination induces a unique inflammatory response in the subventricular zone. J Neuroinflammation 13(1):190 |
| abstractText | 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. |
