Study of molecular mechanisms underlying antidepressant actions of (R)-ketamine

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02846
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Chiba University
• Principal Investigator: Hashimoto Kenji 千葉大学, 社会精神保健教育研究センター, 教授 (10189483)
• Co-Investigator(Kenkyū-buntansha): 藤田 有子 千葉大学, 社会精神保健教育研究センター, 特任助教 (40623591) ; 石間 環 千葉大学, 社会精神保健教育研究センター, 特任助教 (00597130)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ケタミン / うつ病 / 抗うつ薬 / ミエリン / 腸-脳相関

Outline of Final Research Achievements

The anesthetic drug ketamine has been shown to have an immediate antidepressant effect and reduce suicidal ideation in patients with treatment-resistant depression, making it one of the most noteworthy drugs in the field of psychiatry. However, the mechanism behind ketamine's antidepressant action has not yet been clarified. In this study, we explored the mechanism of its antidepressant effects using the optical isomers of ketamine. The results revealed that the resilience-enhancing effects of arketamine are significantly associated with microRNAs in the prefrontal cortex and the spleen-brain axis. Furthermore, it was suggested that the repair of myelin in the prefrontal cortex contributes to the antidepressant effects of arketamine. Additionally, we confirmed that arketamine also improves depressive-like behaviors in mouse models of liver damage.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、これまで治療抵抗性うつ病に対する効果的な治療薬が限られていたことを踏まえると、副作用の少ないアールケタミンが新しい抗うつ薬として期待されます。また、うつ病患者だけでなく、うつ症状を示す身体疾患を持つ患者の治療にも応用可能であり、その社会的意義は非常に大きい。さらに、本研究で見つけたケタミンの作用機序は、新規治療薬の開発に繋がると期待され、研究成果の学術的意義は高い。