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Molecular Mechanism of the Circadian Clock in Hibernating Animals: A Calcium-Based Mechanism of Rhythm Oscillation under Low-Temperature

Planned Research

Project AreaMammalian hibernation biology ~ survival strategies via hypometabolism and hypothermia
Project/Area Number 20H05769
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionCenter for Novel Science Initatives, National Institutes of Natural Sciences

Principal Investigator

Enoki Ryosuke  大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター, 准教授 (00528341)

Co-Investigator(Kenkyū-buntansha) 金 尚宏  名古屋大学, 生命農学研究科(WPI), 特任講師 (80822931)
Project Period (FY) 2020-10-02 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥39,780,000 (Direct Cost: ¥30,600,000、Indirect Cost: ¥9,180,000)
Fiscal Year 2022: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2021: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2020: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Keywords冬眠/休眠 / 概日時計 / 時計遺伝子 / カルシウム / 低温応答 / イメージング / 冬眠 / 光計測 / 温度補償性 / 視交叉上核 / 概日リズム
Outline of Research at the Start

冬眠動物の開始終了や中途覚醒には時刻依存性があるため、生体内には低温でも継続する時計機能が存在すると推察される。この最有力候補は脳深部に存在する概日時計中枢であるが、冬眠中に中枢時計における時計遺伝子の転写振動が継続するか否かは長く議論が続いている。本研究課題では、長期光計測による冬眠動物における中枢時計の振動の検証を行い、さらに低温シグナリング下流の遺伝学的・薬理学的な機能検証を行うことで、冬眠実行の分子ネットワークの核心に迫る。

Outline of Final Research Achievements

In mammalian hibernators, a time dependence of the onset and termination of hibernation has been reported. There might be a timekeeping mechanism in the body that can function at low temperatures, and the most likely candidate is the suprachiasmatic nucleus, the master circadian clock in the brain, but whether the transcriptional rhythm of clock genes continues has long been debated. We previously established long-term imaging of intracellular Ca2+ and transcriptional rhythms in the suprachiasmatic nucleus and found that intracellular circadian Ca2+ rhythms persist even in the suprachiasmatic nucleus, where the key clock gene is lacking. This led to the idea that circadian Ca2+ oscillations might be a timekeeping system with a transcription loop-independent oscillation mechanism. In this project, we attempted to elucidate the dynamics of circadian Ca2+ and transcriptional rhythms in the suprachiasmatic nucleus under low-temperature conditions using optical imaging.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、代表者の榎木が確立した長期光イメージング計測のアドバンテージを最大限活用し、低温環境下での視交叉上核の概日Ca2+リズムと転写リズムのダイナミクスを光イメージングにより解明することを試みた。また分担者の金は、培養細胞を用いたケミカルバイオロジーの手法を駆使して、概日時計におけるCa2+シグナリングの役割を追求した。本研究により、低温でのリズム発振メカニズムを解明し、冬眠休眠実行の分子ネットワークの核心に迫る結果を得た。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (42 results)

All 2023 2022 2021 Other

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Open Access: 6 results,  Peer Reviewed: 6 results) Presentation (30 results) (of which Int'l Joint Research: 6 results,  Invited: 12 results) Remarks (3 results)

  • [Journal Article] 概日時計の温度補償性とCa2+シグナルの役割2023

    • Author(s)
      金尚宏、榎木亮介
    • Journal Title

      低温科学・特集「動物の寒冷適応戦略」

      Volume: 81 Pages: 1-9

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Roles of Ca2+ Signaling in Molecular Clocks2023

    • Author(s)
      Naohiro Kon, Ryosuke Enoki, Hsin-tzu Wang, Yoshitaka Fukada
    • Journal Title

      Sapporo Symposium 2022

      Volume: -

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus2023

    • Author(s)
      Daisuke Ono, Huan Wang, Chi Jung Hung, Hsin-Tzu Wang, Naohiro Kon, Akihiro Yamanaka, Yulong Li, Takashi Sugiyama
    • Journal Title

      Science Advances

      Volume: 9 Issue: 1

    • DOI

      10.1126/sciadv.abq7032

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Singularity response reveals entrainment properties in mammalian circadian clock2023

    • Author(s)
      Kosaku Masuda, Naohiro Kon, Kosuke Iizuka, Yoshitaka Fukada, Takeshi Sakurai and Arisa Hirano
    • Journal Title

      Nature Communications

      Volume: -

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cold-induced Suspension and Resetting of Ca2+ and Transcriptional Rhythms in the Suprachiasmatic Nucleus Neurons2022

    • Author(s)
      Enoki Ryosuke、Kon Naohiro、Shimizu Kimiko、Kobayashi Kenta、Yamaguchi Yoshifumi、Tomomi Nemoto
    • Journal Title

      Biorxiv

      Volume: -

    • DOI

      10.1101/2022.09.18.508357

    • Related Report
      2022 Annual Research Report
    • Open Access
  • [Journal Article] Calcium Rhythm in Mammalian Master Clock2022

    • Author(s)
      ENOKI Ryosuke
    • Journal Title

      Seibutsu Butsuri

      Volume: 62 Issue: 4 Pages: 228-231

    • DOI

      10.2142/biophys.62.228

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real time monitoring of cold Ca2+ dependent transcription and its modulation by NCX inhibitors2022

    • Author(s)
      Wang Hsin-tzu、Miyairi Shiori、Kitamura Miho、Iizuka Kosuke、Asano Yoshimasa、Yoshimura Takashi、Kon Naohiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 17325-17325

    • DOI

      10.1038/s41598-022-22166-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Na+/Ca2+ exchanger mediates cold Ca2+ signaling conserved for temperature-compensated circadian rhythms2021

    • Author(s)
      Kon Naohiro、Wang Hsin-tzu、Kato Yoshiaki S.、Uemoto Kyouhei、Kawamoto Naohiro、Kawasaki Koji、Enoki Ryosuke、Kurosawa Gen、Nakane Tatsuto、Sugiyama Yasunori、Tagashira Hideaki、Endo Motomu、Iwasaki Hideo、Iwamoto Takahiro、Kume Kazuhiko、Fukada Yoshitaka
    • Journal Title

      Science Advances

      Volume: 7 Issue: 18 Pages: 1-12

    • DOI

      10.1126/sciadv.abe8132

    • Related Report
      2021 Annual Research Report 2020 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Circadian Rhythms under Cold Remperature in the Master Clock Neurons2023

    • Author(s)
      榎木亮介, 金尚宏, 山口良文, 根本知己
    • Organizer
      日本生理学会 第100回記念大会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of uncoupling protein 1 (UCP1) in the hypothalamus of Syrian hamster brain2023

    • Author(s)
      張菁圃, 山口良文, 渡邊正知, 根本知己, 榎木亮介
    • Organizer
      日本生理学会 第100回記念大会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A temperature-dependent diabetes-like metabolic state regulated by QIH2023

    • Author(s)
      李明亮, 張菁圃, 根本知己, 榎木亮介
    • Organizer
      日本生理学会 第100回記念大会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] カルシウムシグナルから紐解く概日リズムの生成原理2023

    • Author(s)
      金尚宏
    • Organizer
      日本生理学会 第100回記念大会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 極低温環境下における 概日リズム発振機構2022

    • Author(s)
      榎木亮介, 金尚宏, 山口良文, 根本知己
    • Organizer
      BIOTHERMOLOGY WORKSHOP 2022 &温度生物学若手の会 合同シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 視交叉上核の神経細胞における細胞内カルシウムおよび時計遺伝子転写のリズムは低温により停止しリセットする2022

    • Author(s)
      榎木亮介, 金尚宏, 清水貴美子, 小林憲太, 山口良文, 根本知己
    • Organizer
      第29回 時間生物学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 極低温環境下における概日リズム発振機構2022

    • Author(s)
      榎木亮介, 金尚宏, 山口良文, 根本知己
    • Organizer
      第2回生理研研究会「極限環境適応」
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 冬眠動物の概日時計の分子機構: カルシウムを基軸とした低温リズム発振機構の解明2022

    • Author(s)
      榎木亮介
    • Organizer
      第4回冬眠生物学領域会議
    • Related Report
      2022 Annual Research Report
  • [Presentation] 低温環境下における概日時計中枢のリズム発振機構2022

    • Author(s)
      榎木亮介, 金尚宏, 山口良文, 根本知己
    • Organizer
      温熱研究会2022
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] リズムの無い細胞から紐解く概日時計の成立条件2022

    • Author(s)
      金尚宏
    • Organizer
      第2回生理研研究会「極限環境適応」
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 概日リズムの源流をたどる -時間生物学のディープな世界-2022

    • Author(s)
      金尚宏
    • Organizer
      第4回冬眠生物学領域会議
    • Related Report
      2022 Annual Research Report
  • [Presentation] Roles of Ca2+ Signaling in Molecular Clocks2022

    • Author(s)
      Naohiro Kon
    • Organizer
      Sapporo symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 概日時計の温度補償性 -低温Ca2+シグナルによる生化学振動の制御-2022

    • Author(s)
      金尚宏
    • Organizer
      Neuro2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] An easy-to-use light-needle creating device for single scan volumetric imaging in thick tissue specimens2022

    • Author(s)
      CHANG Ching-Pu, Kohei OTOMO, Yuichi KOZAWA, Hirokazu ISHII, Miwako YAMASAKI, Masahiko WATANABE, Shunichi SATO, Ryosuke ENOKI, Tomomi NEMOTO
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] Optical recording of mitochondrial Ca2+ dynamics in the central circadian clock2022

    • Author(s)
      廣蒼太, 根本知己, 榎木亮介
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 多点走査型2光子顕微鏡を用いた生体脳ボリュームCa2+イメージング2022

    • Author(s)
      安宅光倫, 大友康平, 榎木亮介, 根本知己
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] High-speed imaging of calcium elevations and glutamate release under Aβ oligomers exposure in primary cultured astrocytes2022

    • Author(s)
      中田開人, 大友康平, 石井宏和, 堤元佐, 榎木亮介, 根本知己
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] In vivo calcium imaging reveals neuronal glucose-sensing regulated by body energy status2022

    • Author(s)
      LEE Ming-Liang, CHANG Ching-Pu, NEMOTO Tomomi, ENOKI Ryosuke
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 概日リズム中枢における低温耐性カルシウムリズム2022

    • Author(s)
      榎木亮介, 金尚宏, 山口良文, 根本知己
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Invited
  • [Presentation] 低温環境下で安定かつ柔軟な概日時計中枢カルシウムリズム2022

    • Author(s)
      榎木亮介
    • Organizer
      冬眠休眠研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 概日時計中枢におけるミトコンドリアCa2+濃度動態の光計測2022

    • Author(s)
      廣蒼太, 根本知己, 榎木亮介
    • Organizer
      冬眠休眠研究会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] In vivo calcium imaging reveals dynamic neuronal glucose- sensing in the ventromedial hypothalamus2022

    • Author(s)
      Ming-Liang LEE, Ching Pu CHANG, Tomomi NEMOTO, Ryosuke ENOKI
    • Organizer
      冬眠休眠研究会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 冬眠動物の概日時計の分子機構:カルシウムを基軸とした低温リズム発振機構の解明2022

    • Author(s)
      榎木亮介
    • Organizer
      第3回冬眠生物学領域会議
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 低温環境下で安定かつ柔軟な概日時計中枢カルシウムリズム2022

    • Author(s)
      榎木亮介
    • Organizer
      冬眠休眠研究
    • Related Report
      2020 Annual Research Report
  • [Presentation] 低温環境における概日時計中枢のリズム発振機構2021

    • Author(s)
      榎木亮介
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 極低温環境における概日時計中枢のリズム発振2021

    • Author(s)
      榎木亮介
    • Organizer
      生理学研究所研究会「極限環境適応」
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Invited
  • [Presentation] 概日カルシウムリズムの源流を探る2021

    • Author(s)
      榎木亮介, 廣蒼太, 根本知己
    • Organizer
      生理研研究会「細胞システム理解のためのシグナル応答原理解明の最前線」
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] Visualizing Neuronal Circuits Controlling Circadian and Ultradian Ca2+ Rhythms in Mammals2021

    • Author(s)
      榎木亮介
    • Organizer
      第10回 生理研―霊長研―新潟脳研 合同シンポジウム
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Invited
  • [Presentation] 冬眠動物の概日時計の分子機構:カルシウムを基軸とした低温リズム発振機構の解明2021

    • Author(s)
      榎木亮介
    • Organizer
      第二回冬眠生物学領域会議
    • Related Report
      2020 Annual Research Report
  • [Presentation] 冬眠動物の概日時計の分子機構:カルシウムを基軸とした低温リズム発振機構の解明2021

    • Author(s)
      榎木亮介
    • Organizer
      学術変革領域「冬眠生物学」キックオフミーティング
    • Related Report
      2020 Annual Research Report
  • [Remarks] 個人研究紹介HP

    • URL

      https://ryosukeenoki.wixsite.com/enoki

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/enoki

    • Related Report
      2020 Annual Research Report
  • [Remarks] 個人ページ

    • URL

      https://ryosukeenoki.wixsite.com/enoki

    • Related Report
      2020 Annual Research Report

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Published: 2020-10-30   Modified: 2024-01-30  

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