Brain eicosapentaenoic acid metabolism as a lead for novel therapeutics in major depression

Richard P. Bazinet, Adam H. Metherel, Chuck T. Chen, Saame Raza Shaikh, Agnes Nadjar, Corinne Joffre, Sophie Layé
Brain, Behavior, and Immunity. 2019-07-01; :
DOI: 10.1016/j.bbi.2019.07.001

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Bazinet RP(1), Metherel AH(2), Chen CT(3), Shaikh SR(4), Nadjar A(5), Joffre C(5), Layé S(5).

Author information:
(1)Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada. Electronic address: .
(2)Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
(3)National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, North Bethesda, MD 20852, United States.
(4)Department of Nutrition, Gillings School of Global Public Health & School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
(5)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.

The results of several meta-analyses suggest that eicosapentaenoic acid (EPA) supplementation is therapeutic in managing the symptoms of major depression. It was previously assumed that because EPA is extremely low in the brain it did not cross the blood-brain barrier and any therapeutic effects it exerted would be via the periphery. However, more recent studies have established that EPA does enter the brain, but is rapidly metabolised following entry. While EPA does not accumulate within the brain, it is present in microglia and homeostatic mechanisms may regulate its esterification to phospholipids that serve importantroles in cell signaling. Furthermore, a variety of signaling molecules from EPA have been described in the periphery and they have the potential to exert effects within the brain. If EPA is confirmed to be therapeutic in major depression as a result of adequately powered randomized clinical trials, future research on brain EPA metabolism could lead to the discovery of novel targets for treating or preventing major depression.

Copyright © 2019. Published by Elsevier Inc.

DOI: 10.1016/j.bbi.2019.07.001
PMID: 31278982

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