Disentangling the Molecular Mechanisms of the Antidepressant Activity of Omega-3 Polyunsaturated Fatty Acid: A Comprehensive Review of the Literature.

作者: Martin Hersberger , Gregor E Berger , Suzanne Walitza , Hans O Kalkman

DOI: 10.3390/IJMS22094393

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摘要: Major depressive disorders (MDDs) are often associated with a deficiency in long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), as well signs of low-grade inflammation. Epidemiological and dietary studies suggest that high intake fish, the major source ω-3 PUFAs, is lower rates MDDs. Meta-analyses randomized placebo-controlled PUFAs intervention-trials primarily eicosapentaenoic acid (EPA), but not docosahexaenoic (DHA), responsible for proposed antidepressant effect. In this review, we dissect current biological knowledge on EPA DHA their bioactive lipid metabolites to search pharmacological explanation this, date, unexplained clinical observation. Through enzymatic conversion by cyclooxygenase (COX), lipoxygenase (ALOX), cytochrome P-450 monooxygenase (CYP), metabolized anti-inflammatory pro-resolving mediators. addition, both precursors endocannabinoids, known effects immunomodulation, neuroinflammation, food mood. Finally, crucial structure organization membranes rafts. While most shared these two some distinct features could be identified: (1) The preferential CYP pathway derived eicosanoids; (2) CB2 receptor affinities EPA-derived EPEA its epoxy-metabolite 17,18-EEQ-EA, while DHA-derived endocannabinoids lack such affinities; (3) competition arachidonic (AA) particular glycerophospholipids. AA preferentially incorporated into phosphatidylinositols, mainly phosphatidyl-ethanolamine, -serine -choline. We propose may explain superior activity rich potential novel targets future drugs.

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