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Pharmacol Rev. 2018 Jan;70(1):12-38. doi: 10.1124/pr.117.014092.

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology.

Author information

1
Institut National pour la Recherche Agronomique and Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France (S.L., A.N., C.J.); and Department of Nutritional Sciences, University of Toronto, Ontario, Canada (R.P.B.) sophie.laye@inra.fr.
2
Institut National pour la Recherche Agronomique and Bordeaux University, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France (S.L., A.N., C.J.); and Department of Nutritional Sciences, University of Toronto, Ontario, Canada (R.P.B.).

Abstract

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain.

PMID:
29217656
DOI:
10.1124/pr.117.014092
[Indexed for MEDLINE]
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