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Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis
Oleg Butovsky, … , Steffen Jung, Michal Schwartz
Oleg Butovsky, … , Steffen Jung, Michal Schwartz
Published April 3, 2006
Citation Information: J Clin Invest. 2006;116(4):905-915. https://doi.org/10.1172/JCI26836.
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Research Article Neuroscience Article has an altmetric score of 10

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

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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-γ (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-α production, and overcame blockage of IGF-I production caused by IFN-γ. 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.

Authors

Oleg Butovsky, Gennady Landa, Gilad Kunis, Yaniv Ziv, Hila Avidan, Nadav Greenberg, Adi Schwartz, Igor Smirnov, Ayala Pollack, Steffen Jung, Michal Schwartz

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Figure 4

Effect of MG on the clinical course of EAE depends on their number and activity.

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Effect of MG on the clinical course of EAE depends on their number and a...
On day 7 after induction of EAE in rats as described in Figure 3, their brain lateral ventricles were stereotaxically injected bilaterally with syngeneic MG(–), MG(IFN-γ), or MG(IL-4) (n = 6 per group). One group of rats with EAE remained untreated and served as a control (n = 6). From day 10, BrdU was injected for 2.5 days. Spinal cords were excised 11 days after the first BrdU injection, by which time disease in the rats of all groups was resolved. (A) EAE scores in rats injected stereotaxically with low-dose (1 × 105 cells in 5 μl PBS for 5 minutes) of differently activated MG. (B) EAE scores in rats injected stereotaxically with high doses (5 × 105 cells in 5 μl PBS for 5 minutes). Data are mean α SEM. *P < 0.05, **P < 0.01, ***P < 0.001, MG(IL-4) versus control; Student’s t test. Significant differences (2-factor repeated measures ANOVA) were found between the MG(–) and MG(IL-4) groups: (A) P = 0.0001, F = 61.1; (B) P = 0.0001, F = 79.4.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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