| First Author | Stone S | Year | 2017 |
| Journal | J Neurosci | Volume | 37 |
| Issue | 38 | Pages | 9332-9344 |
| PubMed ID | 28842413 | Mgi Jnum | J:249192 |
| Mgi Id | MGI:6094102 | Doi | 10.1523/JNEUROSCI.1608-17.2017 |
| Citation | Stone S, et al. (2017) NF-kappaB Activation Protects Oligodendrocytes against Inflammation. J Neurosci 37(38):9332-9344 |
| abstractText | NF-kappaB is a key player in inflammatory diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the effects of NF-kappaB activation on oligodendrocytes in MS and EAE remain unknown. We generated a mouse model that expresses IkappaBalphaDeltaN, a super-suppressor of NF-kappaB, specifically in oligodendrocytes and demonstrated that IkappaBalphaDeltaN expression had no effect on oligodendrocytes under normal conditions (both sexes). Interestingly, we showed that oligodendrocyte-specific expression of IkappaBalphaDeltaN blocked NF-kappaB activation in oligodendrocytes and resulted in exacerbated oligodendrocyte death and hypomyelination in young, developing mice that express IFN-gamma ectopically in the CNS (both sexes). We also showed that NF-kappaB inactivation in oligodendrocytes aggravated IFN-gamma-induced remyelinating oligodendrocyte death and remyelination failure in the cuprizone model (male mice). Moreover, we found that NF-kappaB inactivation in oligodendrocytes increased the susceptibility of mice to EAE (female mice). These findings imply the cytoprotective effects of NF-kappaB activation on oligodendrocytes in MS and EAE.SIGNIFICANCE STATEMENT Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. NF-kappaB is a major player in inflammatory diseases that acts by regulating inflammation and cell viability. Data indicate that NF-kappaB activation in inflammatory cells facilitates the development of MS. However, to date, attempts to understand the role of NF-kappaB activation in oligodendrocytes in MS have been unsuccessful. Herein, we generated a mouse model that allows for inactivation of NF-kappaB specifically in oligodendrocytes and then used this model to determine the precise role of NF-kappaB activation in oligodendrocytes in models of MS. The results presented in this study represent the first demonstration that NF-kappaB activation acts cell autonomously to protect oligodendrocytes against inflammation in animal models of MS. |
