NF-κB activation protects oligodendrocytes against inflammation
Item Type: | Article |
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Title: | NF-κB activation protects oligodendrocytes against inflammation |
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Creators Name: | Stone, S. and Jamison, S. and Yue, Y. and Durose, W. and Schmidt-Ullrich, R. and Lin, W. |
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Abstract: | NF-κB is a key player in inflammatory diseases, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). However, the effects of NF-κB activation on oligodendrocytes in MS and EAE remain unknown. We generated a mouse model that expresses IκBαΔN, a super-suppressor of NF-κB, specifically in oligodendrocytes and demonstrated that IκBαΔN expression had no effect on oligodendrocytes under normal conditions (both sexes). Interestingly, we showed that oligodendrocyte-specific expression of IκBαΔN blocked NF-κB activation in oligodendrocytes and resulted in exacerbated oligodendrocyte death and hypomyelination in young, developing mice that ectopically express IFN-γ in the CNS (both sexes). We also showed that NF-κB inactivation in oligodendrocytes aggravated IFN-γ-induced remyelinating oligodendrocyte death and remyelination failure in the cuprizone model (male mice). Moreover, we found that NF-κB inactivation in oligodendrocytes increased the susceptibility of mice to EAE (female mice). These findings imply the cytoprotective effects of NF-κB activation on oligodendrocytes in MS and EAE. |
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Keywords: | EAE, IFN-γ, Multiple Sclerosis, Myelin, NF-κB, Oligodendrocyte, Animals, Mice |
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Source: | Journal of Neuroscience |
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ISSN: | 0270-6474 |
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Publisher: | Society for Neuroscience |
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Volume: | 37 |
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Number: | 38 |
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Page Range: | 9332-9344 |
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Date: | 20 September 2017 |
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Additional Information: | Copyright © 2017 the authors |
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Official Publication: | https://doi.org/10.1523/JNEUROSCI.1608-17.2017 |
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External Fulltext: | View full text on PubMed Central |
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PubMed: | View item in PubMed |
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