Anti-inflammatory effects of omega-3 fatty acids in the brain: Physiological mechanisms and relevance to pharmacology
Pharmacol Rev. 2017-12-07; 70(1): 12-38
DOI: 10.1124/pr.117.014092
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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.
Copyright © 2017 by The American Society for Pharmacology and Experimental
Therapeutics.