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Analysis of regulatory mechanism in retinal circadian rhythm

Research Project

Project/Area Number 17K15574
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionAichi Medical University (2018)
Kindai University (2017)

Principal Investigator

Ikegami Keisuke  愛知医科大学, 医学部, 助教 (10709330)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords網膜 / 概日時計 / 光応答反応 / 視交叉上核 / コルチコステロン / 光感受性 / 活動リズム / 光位相反応 / 時差ぼけ / 松果体 / メラトニン / 環境生理
Outline of Final Research Achievements

The retina transmits light signals to entrain the central circadian clock in the suprachiasmatic nucleus (SCN). Although the SCN regulates the peripheral circadian physiological function, the detail in the retina remains unclear since ambient light is also involved. We first found circadian sensory system to light in the inner retina. Its phase was shifted slowly like the SCN in jet lag, and its pattern were disrupted by adrenalectomy and rescued by glucocorticoid administration, indicating that the SCN rather than ambient light regulates retinal rhythm through glucocorticoid. Expression analysis of neurotransmitter-related genes revealed that diurnal change of GABArelated gene in the RGC mediate retinal photosensitivity rhythm, which is disrupted by retina specific clock deletion. Thus, SCN may regulate GABA-mediated photosensitivity rhythm. This study first demonstrates the entrainment regulatory pathway of retinal circadian rhythm by the SCN.

Academic Significance and Societal Importance of the Research Achievements

網膜からの光情報は概日中枢である視交叉上核に伝達され、体全体の体内時計を統御している。網膜概日リズムは、視交叉上核から誘導された同調因子だけでなく強い同調因子、すなわち環境光の入力も受けるので同調機構は不明のままであったが、本研究により視交叉上核由来の因子が優位であることが判明した。これは、わずかなまたは不規則な光刺激が中枢時計と網膜時計との間の内部非同期を誘発し、視交叉上核へ光信号が不安定になる問題を回避するシステムであると考えられる。さらに、主観的昼にのみ光感受性を低下させる概日リズムの詳細も判明したが、これは昼の日光から網膜が変性して細胞死を起こさないように目を保護すると考えられる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Slow shift of dead zone after an abrupt shift of the light-dark cycle2019

    • Author(s)
      Nagano Mamoru、Ikegami Keisuke、Minami Yoichi、Kanazawa Yuji、Koinuma Satoshi、Sujino Mitsugu、Shigeyoshi Yasufumi
    • Journal Title

      Brain Research

      Volume: 1714 Pages: 73-80

    • DOI

      10.1016/j.brainres.2019.02.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interconnection between circadian clocks system and thyroid function2019

    • Author(s)
      Keisuke Ikegami, Samuel Refetoff, Eve Van Cauter , and Takashi Yoshimura
    • Journal Title

      Nature Review Endocrinology

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of circadian clock modulators from existing drugs2018

    • Author(s)
      T. Katherine Tamai, Yusuke Nakane, Wataru Ota, Akane Kobayashi, Masateru Ishiguro, Naoya Kadofusa, Keisuke Ikegami, Kazuhiro Yagita, Yasufumi Shigeyoshi, Masaki Sudo, Taeko Nishiwaki-Ohkawa, Ayato Sato, & Takashi Yoshimura
    • Journal Title

      EMBO Molecular Medicine

      Volume: - Issue: 5

    • DOI

      10.15252/emmm.201708724

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models2017

    • Author(s)
      Keisuke Ikegami & Takashi Yoshimura
    • Journal Title

      Best Practice & Research Clinical Endocrinology & Metabolism

      Volume: 31 Issue: 5 Pages: 475-485

    • DOI

      10.1016/j.beem.2017.09.002

    • NAID

      120006473528

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of aging on basement membrane of the soleus muscle during recovery following disuse atrophy in rats2017

    • Author(s)
      Kanazawa Yuji、Ikegami Keisuke、Sujino Mitsugu、Koinuma Satoshi、Nagano Mamoru、Oi Yuki、Onishi Tomoya、Sugiyo Shinichi、Takeda Isao、Kaji Hiroshi、Shigeyoshi Yasufumi
    • Journal Title

      Experimental Gerontology

      Volume: 98 Pages: 153-161

    • DOI

      10.1016/j.exger.2017.08.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Retinal circadian rhythm is entrained by the SCN via corticosterone secretion from the adrenal gland2019

    • Author(s)
      Keisuke Ikegami, Mamoru Nagano, Satoru Masubuchi,Yasufumi Shigeyoshi
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 網膜概日リズムは概日時計中枢視交叉上核に影響を及ぼさない2019

    • Author(s)
      池上啓介、増渕悟、重吉康史
    • Organizer
      第14回環境生理プレコングレス
    • Related Report
      2018 Annual Research Report
  • [Presentation] Gating systems of responses to light in mouse inner retina2018

    • Author(s)
      Keisuke Ikegami、Mamoru Nagano、Noriki Sugimoto、Kazumasa Saigoh、Yasufumi Shigeyoshi
    • Organizer
      第94回日本生理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Pineal humoral factors suppress striatal glutamate signal transduction to avoid autism-like mental disorder in mice.2018

    • Author(s)
      池上啓介、毛利彰宏、野田幸裕、増渕悟、重吉康史
    • Organizer
      第25回日本時間生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス網膜の概日光応答リズムは副腎コルチコステロンを介して視交叉上核に制御されている2018

    • Author(s)
      池上啓介、長野護、重吉康史
    • Organizer
      第13回環境生理プレコングレス
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス網膜の概日光応答リズムは副腎コルチコステロンを介して視交叉上核に制御されている2018

    • Author(s)
      池上啓介
    • Organizer
      第13回環境生理プレコングレス
    • Related Report
      2017 Research-status Report
  • [Presentation] マウスにおけるSCNによるコルチコステロンを介した網膜概日光感受性リズムの制御機構の解明2017

    • Author(s)
      池上啓介
    • Organizer
      第24回日本時間生物学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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