n-3 PUFA supplementation benefits microglial responses to myelin pathology

Sci Rep. 2014 Dec 12;4:7458. doi: 10.1038/srep07458.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cells, Cultured
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage*
  • Docosahexaenoic Acids / pharmacology
  • Eicosapentaenoic Acid / administration & dosage*
  • Eicosapentaenoic Acid / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / physiology*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacology
  • Primary Cell Culture


  • Neuroprotective Agents
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid