Elucidation of the neural circuit mechanism of antidepressant-like effect of dietary polyunsaturated fatty acids

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K18402
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology; Psychiatric science
• Research Institution: Tokyo University of Science (2018-2019); National Center of Neurology and Psychiatry (2017)
• Principal Investigator: Yamada Daisuke 東京理科大学, 薬学部薬学科, 助教 (10621302)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 多価不飽和脂肪酸 / うつ様行動 / ドパミン / 側坐核 / 腹側被蓋野

Outline of Final Research Achievements

The present study examined the effect of dietary intake of omega3 (ω3) polyunsaturated fatty acids (PUFA)s on depression-like behavior and the relevant neural circuit in the brain in mice.
Mice fed a diet rich in ω3 PUFAs showed shorter immobility time in the forced swim test (FST) than mice fed a control diet. We also found that dopamine and its metabolites increased in the nuncleus accumbens (NAc) in mice fed the diet rich in ω3 PUFA when compared with mice fed the control diet. Notably, the effects of the diet rich in ω3 PUFA on the immobility time in the FST were abolished by microinjection of dopamine receptor antagonists and cannabinoid CB1 receptor antagonist into the NAc.
These results suggest that modulation of the VTA-NAc dopaminergic pathway is one of the mechanisms by which the diet rich in ω3 PUFAs reduces the immobility behavior in the mouse FST.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

これまで不明なまま残されていたオメガ3多価不飽和脂肪酸(ω3 PUFA)経口摂取による抗うつ様作用の神経メカニズムの一端が明らかとなった。特に側坐核を中心とした神経回路がドパミン神経系を介して活性化されることを示唆する結果を得た。また、ω3 PUFAの抗うつ様作用は、申請者の先行研究恐怖記憶とは異なり、ω3とω6の量比ではなくω3含量によって調節されることが明らかとなった。
本研究の成果は、これまで根拠に乏しかったω3 PUFAを含むサプリメントが脳機能に影響を与える作用メカニズムについての科学的根拠を示すものであり、学術的のみならず社会的な意義も大きいものと考えられる。