Integrated understanding of the light entrainment mechanism encompassing the entire central circadian clock

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21498
• 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: Kanazawa University
• Principal Investigator: Mieda Michihiro 金沢大学, 医学系, 教授 (20296552)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: サーカディアンリズム / 体内時計 / 神経ネットワーク / 視床下部 / 遺伝子操作マウス / 時差

Outline of Final Research Achievements

The central circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is synchronized to the day-night cycle of the external world transmitted from the retina (light entrainment). Light information is first transmitted to the core cells, and then information is sent from the core to the shell, resulting in a phase shift of the entire SCN. The signal transduction mechanisms of core cells have been well studied. However, for light entrainment to be established, the shell, which has a large number of cells and large circadian oscillations, must also undergo a phase shift and become fixed, but this process is not known. We have obtained mice with dramatically altered light-entrainment ability by specific genetic manipulation of the SCN shell, and have analyzed it in detail.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

睡眠に問題を抱える日本人は5人に１人に上る。シフトワークや生活習慣の乱れは、睡眠の主要な制御機構である体内時計に変調をきたし、睡眠障害のみならず、気分障害、肥満、心筋梗塞、がん等、様々な疾患・健康障害のリスクを著しく増大する。中枢体内時計の内因性周期は24時間から少しずれているので、光同調は24時間周期の社会生活を健全に営む上で極めて重要である。また、夜間に人工光を浴びると体内時計が乱れ、睡眠や種々の生体機能に問題が生じる（光害）。本研究により中枢体内時計全体を包括した光同調メカニズムに関する、根本的かつ統合的な理解が得られれば、その学術的・社会的意義は大きい。