Mechanisms underlying aging and disease related circadian dysfunctions by in vivo Miniscope

2024 Fiscal Year Final Research Report

• Project/Area Number: 20KK0229
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Hiroshima University (2022-2024); Waseda University (2020-2021)
• Principal Investigator: Tahara Yu 広島大学, 医系科学研究科(医), 准教授 (80707399)
• Co-Investigator(Kenkyū-buntansha): 中村 孝博 明治大学, 農学部, 専任教授 (00581985) ; 原口 敦嗣 早稲田大学, 理工学術院, 講師(任期付) (80834671) ; 太田 航 横浜市立大学, 医学部, 助教 (80866541)
• Project Period (FY): 2020-10-27 – 2025-03-31
• Keywords: 概日時計 / 老化 / イメージング

Outline of Final Research Achievements

The mechanisms by which the circadian clock becomes disrupted due to aging or various diseases remain largely unexplored. This study aimed to elucidate these mechanisms with a particular focus on the central circadian clock located in the hypothalamus. In order to capture changes in neural activity within the central clock, the primary objective of our research stay at UCLA was to establish a novel imaging technique for the central circadian clock, utilizing the UCLA Miniscope system. Through this international collaborative research, we sought not only to understand the pathophysiology of several models, including the senescence-accelerated mouse model, the adenine-induced chronic kidney disease model, the caffeine-induced circadian phase-delay model, the bipolar disorder model with circadian dysfunction, and the jet lag-induced reproductive cycle disruption model, but also to uncover the underlying mechanisms of circadian clock modulation in these contexts.

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

規則正しい生活と共に、概日リズム、概日時計を健康に保つことは、疾患の発症や予防に役立つことがわかってきた。一方で、疾患に罹患することで概日時計が乱れ、それが疾患の進行を早めることも分かりつつある。しかし、疾患や加齢における概日時計の乱れのメカニズムは不明な点が多く、本研究では、概日時計の中枢である視交叉上核のイメージング手法を基に、様々なモデルマウスを駆使し、その謎に迫った。