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J Clin Invest. 2006 Apr;116(4):905-15. Epub 2006 Mar 23.

Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis.

Author information

1
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Abstract

The role of activated microglia (MG) in demyelinating neurodegenerative diseases such as multiple sclerosis is controversial. Here we show that high, but not low, levels of IFN-gamma (a cytokine associated with inflammatory autoimmune diseases) conferred on rodent MG a phenotype that impeded oligodendrogenesis from adult neural stem/progenitor cells. IL-4 reversed the impediment, attenuated TNF-alpha production, and overcame blockage of IGF-I production caused by IFN-gamma. In rodents with acute or chronic EAE, injection of IL-4-activated MG into the cerebrospinal fluid resulted in increased oligodendrogenesis in the spinal cord and improved clinical symptoms. The newly formed oligodendrocytes were spatially associated with MG expressing MHC class II proteins and IGF-I. These results point to what we believe to be a novel role for MG in oligodendrogenesis from the endogenous stem cell pool.

PMID:
16557302
PMCID:
PMC1409740
DOI:
10.1172/JCI26836
[Indexed for MEDLINE]
Free PMC Article

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