title: n-3 PUFA supplementation benefits microglial responses to myelin pathology.
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-α from 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.
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Songela
authors.initials: S
authors.lastname: Chen
authors.affiliation: 1] Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA [2] Xiangya Third Hospital, Central South University, Changsha, Hunan 410013, China.
authors.forename: Haiyue
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1] Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA [2] State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Pu
authors.affiliation: 1] Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA [2] State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Li
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
authors.affiliation: 1] Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA [2] State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Liou
authors.affiliation: 1] Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA [2] State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D061251:Primary Cell Culture
chemical_list: D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid