Abstract
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 language | English |
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Pages (from-to) | 105-21 |
Number of pages | 17 |
Journal | GLIA |
Volume | 64 |
Issue number | 1 |
Early online date | 4 Sept 2015 |
DOIs | |
Publication status | Published - Jan 2016 |
Keywords
- 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
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't