Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis
Open accessAbstract
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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CD11c+ microglia are known to increase in chronic inflammatory and neurodegenerative conditions as well as during development.
“CD11c+ microglia are known to increase in chronic inflammatory and neurodegenerative conditions as well as during development [76–83]”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [76]
The Discussion (page unavailable) mentions a CD11c+ promoter only in describing preliminary transgenic-mouse experiments; it does not report an increase in CD11c+ microglia. The paper discusses microglial changes in EAE, but the passages found do not address CD11c+ microglia increasing across chronic inflammatory or neurodegenerative conditions or during development (searched: CD11c and developmental and disease terms). (LLM, conf=0.76)
Experimental — accuracy not yet measuredM2 microglia express genes including IGF-1.
“We found that M1 microglia express a high level of inflammatory-related transcripts including Ccl2, Ccl3, Ccl5, whereas M2 microglia express genes including IGF-1 (Supplementary Fig. 10a,b), which play a role in tissue development and neural cell renewal28.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [28]
M1 microglia express a high level of inflammatory-related transcripts including Ccl2, Ccl3, Ccl5.
“We found that M1 microglia express a high level of inflammatory-related transcripts including Ccl2, Ccl3, Ccl5, whereas M2 microglia express genes including IGF-1 (Supplementary Fig. 10a,b), which play a role in tissue development and neural cell renewal28.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [28]
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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
- Published
- 2006-03-23
- Volume
- 116
- Issue
- 4
- Pages
- 905-915
- ISSN
- 0021-9738 (ISSN-L)
- 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 › Pathology and Forensic Medicine › 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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