Cited by 262Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

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

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Butovsky, O.·2006·Journal of Clinical Investigation

DOI 10.1172/jci26836PMC PMC1409740

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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-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.

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Authors: Butovsky, O.
Affiliations: Weizmann Institute of Science (IL)
Corresponding author: Butovsky, O.
ORCID: Butovsky, O.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2006-03-23
Volume: 116
Issue: 4
Pages: 905-915
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci26836
PMC: PMC1409740
OpenAlex: W2145533845
Cited by: 261
References: 71
Citations by year: 2026: 2 · 2025: 5 · 2024: 11 · 2023: 15 · 2022: 8 · 2021: 7 · 2020: 14 · 2019: 18 · 2018: 10 · 2017: 11 · 2016: 15 · 2015: 16 · 2014: 16 · 2013: 16 · 2012: 16
FWCI: 13.58
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: microglia, oligodendrogenesis, multiple sclerosis, experimental autoimmune encephalomyelitis, interferon-gamma, IL-4, TNF-α, insulin-like growth factor I, neural stem/progenitor cells, demyelination, MHC class II, oligodendrocytes, cerebrospinal fluid injection, neuroinflammation
MeSH terms: Animals, Cells, Cultured, Cerebral Ventricles, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Interferon-gamma, Male, Mice, Inbred C57BL, Multiple Sclerosis, Oligodendroglia, Rats, Inbred Lew, Recombinant Proteins, Stem Cells, Interleukin-4, Microglia, Mice, Knockout, Mice, Rats

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

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