Basic medicine of resilience

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19351
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Kobe University
• Principal Investigator: Takumi Toru 神戸大学, 医学研究科, 教授 (00222092)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: レジリエンス / リン酸化 / 時計タンパク質

Outline of Final Research Achievements

A mouse model was created in which phosphorylation mutations in the clock protein PER2 express sleep-wake rhythm mutations and mood state mutations (depression, resilience). Although lithium (mood stabilizer) is a known kinase inhibitor, we identified CMGC protein kinase as upstream kinases of PER2 phosphorylation based on a comprehensive screening of kinase proteins. Furthermore, we identified PPAR gamma as a downstream molecule of PER2 phosphorylation, suggesting that PER2 phosphorylation is related not only to sleep and mood but also to metabolism.

Free Research Field

病態医化学

Academic Significance and Societal Importance of the Research Achievements

現在気分障害のマウスモデルとしては、社会的敗北ストレスによるサセプタブルもしくはレジリエンスモデルが知られているが、その分子的基盤は不明である。本レジリエンスモデルマウスは、分子的メカニズムが明らかなモデルマウスで、これまでのモデルとは一線を画する新規マウスモデルである。