• Zhuoran Zhu, Zhoubin Tan, Yan Li, Hongyan Luo, Xinwu Hu, Ming Tang, Jürgen Hescheler, Yangling Mu, and Lanqiu Zhang.
• Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
• Nutrition. 2015 Jul 1; 31 (7-8): 1025-30.

ObjectiveSupplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA), recently has become popular for the amelioration of depression; however the molecular mechanism of DHA action remains unclear. The aim of this study was to investigate the mechanism underlying the antidepressant effect of DHA by evaluating Gsα localization in lipid raft and the activity of adenylate cyclase in an in vitro glioma cell model.MethodsLipid raft fractions from C6 glioma cells treated chronically with DHA were isolated by sucrose gradient ultracentrifugation. The content of Gsα in lipid raft was analyzed by immunoblotting and colocalization of Gsα with lipid raft was subjected to confocal microscopic analysis. The intracellular cyclic adenosine monophosphate (cAMP) level was determined by cAMP immunoassay kit.ResultsDHA decreased the amount of Gsα in lipid raft, whereas whole cell lysate Gsα was not changed. Confocal microscopic analysis demonstrated that colocalization of Gsα with lipid raft was decreased, whereas DHA increased intracellular cAMP accumulation in a dose-dependent manner. Interestingly, we found that DHA increased the lipid raft level, instead of disrupting it.ConclusionsThe results of this study suggest that DHA may exert its antidepressant effect by translocating Gsα from lipid raft and potentiating the activity of adenylate cyclase. Importantly, the reduced Gsα in lipid raft by DHA is independent of disruption of lipid raft. Overall, the study provides partial preclinical evidence supporting a safe and effective therapy using DHA for depression.Copyright © 2015 Elsevier Inc. All rights reserved.

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