N-3 PUFA supplementation benefits microglial responses to myelin pathology
DOI
10.1038/srep07458
Document Type
Journal Article
Publication Date
12-12-2014
Publication Title
Scientific Reports
Volume
4
Abstract
Microglia represent rational but challenging targets for improving white matter integrity because of their dualistic protective and toxic roles. The present study examines the effect of Omega-3 polyunsaturated fatty acids (n-3 PUFAs) on microglial responses to myelin pathology in primary cultures and in the cuprizone mouse model of multiple sclerosis (MS), a devastating demyelination disease. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main forms of n-3 PUFAs in the brain, inhibited the release of nitric oxide and tumor necrosis factor- αfrom primary microglia upon IFN-γ and myelin stimulation. DHA and EPA also enhanced myelin phagocytosis in vitro. Therefore, n-3 PUFAs can inhibit inflammation while at the same time enhancing beneficial immune responses such as microglial phagocytosis. In vivo studies demonstrated that n-3 PUFA supplementation reduced cuprizone-induced demyelination and improved motor and cognitive function. The positive effects of n-3 PUFAs were accompanied by a shift in microglial polarization toward the beneficial M2 phenotype both in vitro and in vivo. These results suggest that n-3 PUFAs may be clinically useful as immunomodulatory agents for demyelinating diseases through a novel mechanism involving microglial phenotype switching.
Open Access
Gold
Repository Citation
Chen, S., Zhang, H., Pu, H., Wang, G., Li, W., Leak, R., Chen, J., Liou, A., & Hu, X. (2014). N-3 PUFA supplementation benefits microglial responses to myelin pathology. Scientific Reports, 4. https://doi.org/10.1038/srep07458