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

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 6

Rats injected intraventricularly with MG(IL-4) exhibit increased microglial proliferation and MHC class II (MHC-II) expression.

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Rats injected intraventricularly with MG(IL-4)...
The spinal cords analyzed in Figure 3 were also examined for microgliogenesis. (A) Quantitative analysis of IB4+ and IB4+/MHC class II+ cells colabeled with BrdU+ (mean α SEM) from both gray matter and white matter (n = 8 per group). *P < 0.05, ***P < 0.001 versus PBS; 2-tailed Student’s t test. (B) Representative confocal microscopy of longitudinal sagittal sections of spinal cords (T8–T9) stained with BrdU and costained with IB4 for MG and MHC class II 21 days after injection with PBS or with MG(IL-4). The most abundant populations of BrdU+ cells were immunoreactive to IB4 in both control and MG(IL-4)-injected rats. Significantly more MHC class II+ cells were seen, especially in the gray matter, in slices from MG(IL-4)-injected rats than from those of PBS-injected control rats. Note that the images are from areas that include both gray matter and white matter; dashed line shows the border between the 2 areas. (C and D) Most of the newly formed MG (IB4+/BrdU+) in MG(IL-4)-treated rats coexpressed (C) MHC class II and (D) IGF-I (arrows).