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

Research Project

Project/Area Number 20K21498
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionKanazawa University

Principal Investigator

Mieda Michihiro  金沢大学, 医学系, 教授 (20296552)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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 / 概日リズム / 視交叉上核 / 局所神経ネットワーク / 光同調 / 中枢体内時計 / バソプレシン
Outline of Research at the Start

社会生活を健全に営む上で、内因性周期が24時間からずれている中枢体内時計をきっちりと外界の昼夜サイクルに同調させること(光同調)が極めて重要である。中枢体内時計・視交叉上核(SCN)はcoreとshellの領域に分けられ、前者は網膜からの光情報の入力部、後者は概日(サーカディアン)リズムを発振する主要な振動部と言える。coreの光応答については研究が進んでいる。しかし光同調の成立にはshellでも概日リズム位相がシフトして固定される必要があるが、この機構は明らかでない。応募者はこの問題を解く突破口となるモデルマウスを得たので、解析し、中枢体内時計全体を包括した光同調メカニズムの理解を目指す。

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.

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。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results) (of which Invited: 2 results)

  • [Journal Article] Cell type-specific genetic manipulation and impaired circadian rhythms in ViptTA knock-in mice2022

    • Author(s)
      Peng Y, Tsuno Y, Matsui A, Hiraoka Y, Tanaka K, Horike S, Daikoku T, Mieda M
    • Journal Title

      Front Physiol

      Volume: 13 Pages: 895633-895633

    • DOI

      10.3389/fphys.2022.895633

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior2021

    • Author(s)
      Maejima Takashi、Tsuno Yusuke、Miyazaki Shota、Tsuneoka Yousuke、Hasegawa Emi、Islam Md Tarikul、Enoki Ryosuke、Nakamura Takahiro J.、Mieda Michihiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 6 Pages: 1-18

    • DOI

      10.1073/pnas.2010168118

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice2021

    • Author(s)
      Hasan Nazmul、Nagata Naoto、Morishige Jun-ichi、Islam Md Tarikul、Jing Zheng、Harada Ken-ichi、Mieda Michihiro、Ono Masanori、Fujiwara Hiroshi、Daikoku Takiko、Fujiwara Tomoko、Maida Yoshiko、Ota Tsuguhito、Shimba Shigeki、Kaneko Shuichi、Fujimura Akio、Ando Hitoshi
    • Journal Title

      Molecular Metabolism

      Volume: 49 Pages: 101202-101202

    • DOI

      10.1016/j.molmet.2021.101202

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 増大特集 脳の発振現象-基礎から臨床へ 中枢時計・視交叉上核によるサーカディアンリズム発振のメカニズム2020

    • Author(s)
      三枝理博
    • Journal Title

      BRAIN and NERVE

      Volume: 72 Issue: 11 Pages: 1143-1150

    • DOI

      10.11477/mf.1416201667

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2020-11-01
    • Related Report
      2020 Research-status Report
  • [Presentation] Critical roles of AVP neurons in the central circadian clock of the SCN2022

    • Author(s)
      Mieda M
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] AVP neurons of the SCN act as the principal circadian pacemaker cells in vivo2022

    • Author(s)
      Tsuno Y, Peng Y, Daikoku T, Horike S, Yamagata K, Maejima T, Mieda M
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior.2021

    • Author(s)
      Maejima T, Tsuno Y, Miyazaki S, Tsuneoka Y, Hasegawa E, Islam MT, Enoki R, Nakamura TJ, Mieda M.
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Cellular clocks of AVP neurons regulate the cellular circadian period of VIP neurons in the mouse SCN in vivo2021

    • Author(s)
      Tsuno Y, Peng Y, Daikoku T, Horike S, Mieda M
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Vasopressin neurons in the paraventricular hypothalamus induce wakefulness via orexin neurons2021

    • Author(s)
      Islam MT, Rumpf F, Tsuno Y, Maejima T, Mieda M.
    • Organizer
      第98回日本生理学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 中枢時計におけるバソプレシン産生ニューロンの機能2020

    • Author(s)
      三枝理博
    • Organizer
      第27回日本時間生物学会学術大会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-08-03   Modified: 2023-01-30  

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