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| Item Type: | Article |
|---|---|
| Title: | Reversible neural stem cell niche dysfunction in a model of multiple sclerosis |
| Creators Name: | Rasmussen, S., Imitola, J., Ayuso-Sacido, A., Wang, Y., Starossom, S.C., Kivisäkk, P., Zhu, B., Meyer, M., Bronson, R.T., Garcia-Verdugo, J.M. and Khoury, S.J. |
| Abstract: | OBJECTIVE: The subventricular zone (SVZ) of the brain constitutes a niche for neural stem and progenitor cells that can initiate repair after central nervous system (CNS) injury. In a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE), the neural stem cells (NSCs) become activated and initiate regeneration during acute disease, but lose this ability during the chronic phases of disease. We hypothesized that chronic microglia activation contributes to the failure of the NSC repair potential in the SVZ. METHODS: Using bromodeoxyuridine injections at different time points during EAE, we quantified the number of proliferating and differentiating progenitors, and evaluated the structure of the SVZ by electron microscopy. In vivo minocycline treatment during EAE was used to address the effect of microglia inactivation on SVZ dysfunction. RESULTS: In vivo treatment with minocycline, an inhibitor of microglia activation, increases stem cell proliferation in both naive and EAE animals. Minocycline treatment decreases cortical and periventricular pathology in the chronic phase of EAE, improving the proliferation of Sox2 stem cells and NG2 oligodendrocyte precursors cells originating in the SVZ and their differentiation into mature oligodendrocytes. INTERPRETATION: These data suggest that failure of repair observed during chronic EAE correlates with microglia activation and that treatments targeting chronic microglial activation have the potential for enhancing repair in the CNS. |
| Keywords: | Animal Disease Models, Anti-Bacterial Agents, Bromodeoxyuridine, Cell Count, Cell Movement, Cell Proliferation, Experimental Autoimmune Encephalomyelitis, Microglia, Minocycline, Multiple Sclerosis, Myelin Proteolipid Protein, Neural Stem Cells, Oligodendroglia, Peptide Fragments, Secondary Prevention, Stem Cell Niche, Time Factors, Transmission Electron Microscopy, Animals, Mice |
| Source: | Annals of Neurology |
| ISSN: | 1531-8249 |
| Publisher: | Wiley-Blackwell |
| Volume: | 69 |
| Number: | 5 |
| Page Range: | 878-891 |
| Date: | May 2011 |
| Additional Information: | Copyright © 2011 American Neurological Association. |
| Official Publication: | https://doi.org/10.1002/ana.22299 |
| External Fulltext: | View full text on external repository or document server |
| PubMed: | View item in PubMed |
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