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NF-κB activation protects oligodendrocytes against inflammation

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Item Type:Article
Title:NF-κB activation protects oligodendrocytes against inflammation
Creators Name:Stone, S. and Jamison, S. and Yue, Y. and Durose, W. and Schmidt-Ullrich, R. and Lin, W.
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.
Keywords:EAE, IFN-γ, Multiple Sclerosis, Myelin, NF-κB, Oligodendrocyte, Animals, Mice
Source:Journal of Neuroscience
ISSN:0270-6474
Publisher:Society for Neuroscience (U.S.A.)
Volume:37
Number:38
Page Range:9332-9344
Date:20 September 2017
Additional Information:Copyright © 2017 the authors
Official Publication:https://doi.org/10.1523/JNEUROSCI.1608-17.2017
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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