NF-κB activation protects oligodendrocytes against inflammation
Authors
- S. Stone
- S. Jamison
- Y. Yue
- W. Durose
- R. Schmidt-Ullrich
- W. Lin
Journal
- Journal of Neuroscience
Citation
- J Neurosci 37 (38): 9332-9344
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.