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 IκBβΔN, a super-suppressor of NF-κB, specifically in oligodendrocytes and demonstrated that IκBβΔN expression had no effect on oligodendrocytes under normal conditions (both sexes). Interestingly, we showed that oligodendrocyte-specific expression of IκBβΔN blocked NF-κB activation in oligodendrocytes and resulted in exacerbated oligodendrocyte death and hypomyelination in young, developing mice that express IFN-κ ectopically in the CNS (both sexes). We also showed that NF-κB inactivation in oligodendrocytes aggravated IFN-κ-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.
Bibliographical noteFunding Information:
Received June 9, 2017; revised Aug. 7, 2017; accepted Aug. 16, 2017. Authorcontributions:W.L.designedresearch;S.S.,S.J.,Y.Y.,W.D.,andW.L.performedresearch;R.S.-U.contributed unpublished reagents/analytic tools; S.S., S.J., and W.L. analyzed data; S.S. and W.L. wrote the paper. W.L. is supported by the National Institutes of Health (Grants NS094151 and NS073132) and the National Multiple Sclerosis Society (Grant RG 5239-A-3). We thank Dr. Klaus-Armin Nave (Max Planck Institute of Experimental Medicine,Göttingen,Germany)forprovidingtheCNP/CremiceandDr.M.A.AryanNamboodiri(UniformedServices University of the Health Sciences, Bethesda, MD) for providing the antibody against aspartoacylase. The authors declare no competing financial interests. Correspondence should be addressed to Wensheng Lin, Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, WMBB4-140, Minneapolis, MN 55455. E-mail: email@example.com. DOI:10.1523/JNEUROSCI.1608-17.2017 Copyright © 2017 the authors 0270-6474/17/379332-13$15.00/0
© 2017 the authors.
- Multiple sclerosis