Identification of determinants of depression pathogenesis and treatment

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kyoto University
• Principal Investigator: Nagayasu Kazuki 京都大学, 薬学研究科, 助教 (00717902)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: セロトニン / うつ病 / 光遺伝学 / ウイルスベクター

Outline of Final Research Achievements

Using optogenetic techniques, we investigated whether chronic activation of serotonergic neurons in the dorsal raphe nucleus (DRN) causes persistent antidepressant effects. We found that chronic activation of DRN serotonergic neurons induces persistent antidepressant effects and that the mechanism is selective activation of the pleasant experience neural ensemble in the hippocampus. Furthermore, we found that the median raphe nucleus (MRN) serotonergic neurons are responsible for unpleasant emotions, in contrast to the DRN serotonergic neurons. These results suggest that among serotonergic neurons, the DRN serotonergic neurons play a central role in antidepressant effects and that the MRN serotonergic neurons may have an antagonistic role.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究により明らかにされた、背側縫線核セロトニン神経と正中縫線核セロトニン神経の機能的対照性と、背側縫線核セロトニン神経による持続的な抗うつ作用を併せて考えると、セロトニン神経伝達を個別に制御が可能な薬剤を開発することで、既存薬を超える抗うつ薬開発が可能になると考えられることから、本研究によりその基礎的知見が得られたものと考えられる。