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Elucidation of the mechanism of thermoregulation by the circadian clock

Research Project

Project/Area Number 21H02526
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionNagoya University

Principal Investigator

Daisuke Ono  名古屋大学, 環境医学研究所, 講師 (30634224)

Co-Investigator(Kenkyū-buntansha) 中村 孝博  明治大学, 農学部, 専任教授 (00581985)
山口 裕嗣  名古屋大学, 環境医学研究所, 特任助教 (10542970)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2022: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywords概日リズム / 神経回路 / 視床下部 / 視交叉上核 / 休眠 / 代謝 / 睡眠・覚醒 / 体温調節 / 光操作 / 体温 / 日内休眠 / 光計測 / イメージング
Outline of Research at the Start

哺乳類における概日時計の中枢は、視床下部に位置する「視交叉上核」に存在し、時計遺伝子群の転写・翻訳を介したフィードバックループにより24時間のリズムが生成される。そのリズムは外界の明暗環境に同調し、最終的に睡眠・覚醒や体温リズムなど様々な生理機能の時間的調節を行う。これまで研究から、現象的に概日時計がこれらの生理機能を調節している事が示されてきたが、実際どの神経回路がどの生理機能の時間調節に関与するのかは不明であった。本研究では、光遺伝学、光イメージング、神経トレーシング、ゲノム編集など様々な最新の技術を組み合わせ、概日時計による体温調節メカニズムを神経回路レベルで明らかにする。

Outline of Final Research Achievements

The purpose of this study was to elucidate the mechanism of thermoregulation by the circadian clock at the neural circuit level using mice. We found that 24 hours of fasting in a low-temperature environment causes a decrease in body temperature below 30 degrees Celsius, and that this hypothermic state is regulated by the circadian clock. Using optogenetics and optical imaging techniques, we also revealed the circuits and molecules associated with the output pathway from the suprachiasmatic nucleus, the central circadian clock, that are involved in inducing hypothermia.

Academic Significance and Societal Importance of the Research Achievements

冬眠や休眠は、動物が厳しい環境を生き抜くために代謝を能動的に低下させるシステムである。この分子・神経メカニズムの解明には、多くの医学的および社会的意義がある。例えば、低酸素症や心停止後の治療、臓器移植時の臓器保存など、救急医療の発展に繋がる。特に、心臓手術や脳外科手術中の低体温療法の改善により、患者の予後が大幅に向上する可能性がある。また、長期間の宇宙旅行における宇宙飛行士の健康維持や、災害時の生命維持技術の開発にも役立つ可能性がある。さらに、代謝をコントロールする技術により、老化の遅延や生活習慣病の予防にも貢献する。本研究成果は、医学的進歩と社会的福祉の向上に大きく寄与するものである

Report

(3 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (25 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Remarks (3 results)

  • [Int'l Joint Research] 北京大学(中国)

    • 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] Serotonergic neurons control cortical neuronal intracellular energy dynamics by modulating astrocyte-neuron lactate shuttle2023

    • Author(s)
      Natsubori Akiyo、Hirai Shinobu、Kwon Soojin、Ono Daisuke、Deng Fei、Wan Jinxia、Miyazawa Momoka、Kojima Takashi、Okado Haruo、Karashima Akihiro、Li Yulong、Tanaka Kenji F.、Honda Makoto
    • Journal Title

      iScience

      Volume: 26 Issue: 1 Pages: 105830-105830

    • DOI

      10.1016/j.isci.2022.105830

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Level of constitutively expressed BMAL1 affects the robustness of circadian oscillations2022

    • Author(s)
      Padlom Apirada、Ono Daisuke、Hamashima Rio、Furukawa Yuko、Yoshimura Takashi、Nishiwaki-Ohkawa Taeko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 19519-19519

    • DOI

      10.1038/s41598-022-24188-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neural circuits in the central circadian clock and their regulation of sleep and wakefulness in mammals2022

    • Author(s)
      Ono, D.
    • Journal Title

      Neuroscience Research

      Volume: 182 Pages: 44932-44932

    • DOI

      10.1016/j.neures.2022.05.005

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus2022

    • Author(s)
      Rahaman Sheikh Mizanur、Chowdhury Srikanta、Mukai Yasutaka、Ono Daisuke、Yamaguchi Hiroshi、Yamanaka Akihiro
    • Journal Title

      Frontiers in Neuroscience

      Volume: 16 Pages: 808754-808754

    • DOI

      10.3389/fnins.2022.877054

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditional Knockout of Bmal1 in Corticotropin-Releasing Factor Neurons Does Not Alter Sleep-Wake Rhythm in Mice.2022

    • Author(s)
      Hung CJ, Yamanaka A, *Ono D.
    • Journal Title

      Front Neurosci

      Volume: 15 Pages: 808754-808754

    • DOI

      10.3389/fnins.2021.808754

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The food-entrainable oscillator is a complex of non-SCN activity bout oscillators uncoupled from the SCN circadian pacemaker2021

    • Author(s)
      Nishide, S., Suzuki, Y., Ono, D., Honma, S., and Honma, K.
    • Journal Title

      Journal of Biological Rhythms

      Volume: 36(6) Issue: 6 Pages: 575-588

    • DOI

      10.1177/07487304211047937

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CHRONO and DEC1/DEC2 compensate for lack of CRY1/CRY2 in expression of coherent circadian rhythm but not in generation of circadian oscillation in the neonatal mouse SCN.2021

    • Author(s)
      Ono D, Honma KI, Schmal C, Takumi T, Kawamoto T, Fujimoto K, Kato Y, Honma S.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 19240-19240

    • DOI

      10.1038/s41598-021-98532-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: Development of Circadian Clock Functions2021

    • Author(s)
      Myung Jihwan、Nakamura Takahiro J.、Jones Jeff R.、Silver Rae、Ono Daisuke
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 735007-735007

    • DOI

      10.3389/fnins.2021.735007

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reversible modulation of circadian time with chronophotopharmacology2021

    • Author(s)
      Kolarski Dusan、Mir-Vinyals Carla、Sugiyama Akiko、Srivastava Ashutosh、Ono Daisuke、Nagai Yoshiko、Iida Mui、Itami Kenichiro、Tama Florence、Szymanski Wiktor、Hirota Tsuyoshi、Feringa Ben L.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3164-3164

    • DOI

      10.1038/s41467-021-23301-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock2021

    • Author(s)
      Ono Daisuke、Honma Ken-ichi、Honma Sato
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 650154-650154

    • DOI

      10.3389/fnins.2021.650154

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus2023

    • Author(s)
      小野大輔,Huan Wang, Chi Jung Hung, Hsin-tzu Wang, 山中章弘,Yulong Li, 杉山崇
    • Organizer
      第100回日本生理学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] The central circadian clock regulates wakefulness via CRF neurons in the hypothalamus2022

    • Author(s)
      Ono, D.
    • Organizer
      Journal of Neurochemistry Mini-meet
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Network-driven intracellular cAMP coordinates circadian rhythm in mouse suprachiasmatic nucleus2022

    • Author(s)
      Ono, D., Wang, H., Hung, J.C., Wang, T.H., Kon, N., Yamanaka, A., Li, Y., and Sugiyama, T.
    • Organizer
      International Symposium on Chronogenesis
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Network-driven intracellular cAMP coordinates circadian rhythm in mouse suprachiasmatic nucleus2022

    • Author(s)
      Ono, D.
    • Organizer
      第29回日本時間生物学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Network driven circadian cAMP rhythm in the mouse suprachiasmatic nucleus2022

    • Author(s)
      Ono, D., Hung, J.C.,Yamanaka. A., and Sugiyama, T.
    • Organizer
      NEURO2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] Circadian output pathways from the suprachiasmatic nucleus that control sleep and wakefulness2022

    • Author(s)
      Ono, D.
    • Organizer
      第99回日本生理学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 中枢概日時計細胞の同期・非同期状態と生後発達2021

    • Author(s)
      小野大輔
    • Organizer
      第72回コロイドおよび界面化学討論会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] The central circadian clock regulates wakefulness via CRF neurons in the hypothalamus2021

    • Author(s)
      Ono, D., Mukai, Y., Hung, C. J, Chowdury, S., Sugiyama, T., and Yamanaka A.
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Optical recording of intracellular cAMP rhythms in the mouse suprachiasmatic nucleus2021

    • Author(s)
      小野大輔,Chi Jung Hung,杉山崇,山中章弘
    • Organizer
      第28回日本時間生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The suprachiasmatic nucleus regulates wakefulness via CRF neurons in the hypothalamus2021

    • Author(s)
      Ono, D.
    • Organizer
      5th Asian forum on chronobiology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 体内時計中枢における細胞内 cAMP の機能を解明

    • URL

      https://www.med.nagoya-u.ac.jp/medical_J/research/pdf/Sci_230105.pdf

    • Related Report
      2022 Annual Research Report
  • [Remarks] My home page

    • URL

      https://daiono14.wixsite.com/circadianrhythm

    • Related Report
      2022 Annual Research Report
  • [Remarks] 研究ユニットHP

    • URL

      https://daiono14.wixsite.com/circadianrhythm

    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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