Identification of antidepressive serotonin projection as a possible target of cell transplantation therapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14919
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• 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): 2018-04-01 – 2020-03-31
• Keywords: セロトニン / 抗うつ薬 / 光遺伝学

Outline of Final Research Achievements

Major depression and anxiety disorders are a social and economic burden worldwide. Serotonergic signaling has been implicated in the pathophysiology of these disorders and thus has been a crucial target for pharmacotherapy. However, the precise mechanisms underlying these disorders are still unclear. Here, we used species-optimized lentiviral and adeno-associated viral vectors, capable of efficient and specific transduction of serotonergic neurons in mice and rats for elucidation of serotonergic roles in anxiety-like behaviors and active coping behavior in both species. By using these vectors, we found that activation of dorsal raphe serotonin neurons elicited rapid antidepressant-like effect in mice and rat and that activation of VTA-projecting dorsal raphe serotonin neurons induced strong reward-like effect.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

セロトニン神経自体も、その受容体であるセロトニン受容体も、脳全体に広く投射、分布していることから、セロトニン神経全体の活性化や、脳全体のセロトニン受容体の刺激/阻害のみでは、副作用なく抗うつ作用のみを引き起こすことは困難である。本研究により、各セロトニン神経投射の個別の機能解析が可能となり、報酬効果に関わる投射の同定に至ったことから、今後同様の解析を継続することで、副作用なく抗うつ作用のみを引き起こす医薬品の開発に資する知見を得ることができると考えられる。