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Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3(-/-) mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3(-/-) mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3(-/-) mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.

Original publication

DOI

10.1002/glia.22906

Type

Journal article

Journal

Glia

Publication Date

01/2016

Volume

64

Pages

105 - 121

Keywords

galectin-3, multiple sclerosis, subventricular zone, Adolescent, Adult, Aged, Animals, Brain, Cell Movement, Child, Female, Galectin 3, Humans, Male, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Multiple Sclerosis, Nervous System Autoimmune Disease, Experimental, Neural Stem Cells, Neurogenesis, Poliomyelitis, Stem Cell Niche, Theilovirus, Young Adult