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Elucidation of the mechanism of action of Q-neurons

Research Project

Project/Area Number 21K19287
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 45:Biology at organismal to population levels and anthropology, and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

Sakurai Takeshi  筑波大学, 医学医療系, 教授 (60251055)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords冬眠 / 人工冬眠 / 体温調節 / 視床下部 / 体温制御 / 体温 / 代謝
Outline of Research at the Start

研究代表者らが見出した視床下部の特定の神経細胞集団(Qニューロン)を操作することによる冬眠様の低代謝状態の作用機構を明らかにし、Qニューロンの生体における活動様式を解明およびQニューロンの発現遺伝子を明らかにすることを目的に、視床下部背内側核におけるターゲットニューロンの同定、生理的条件下におけるQニューロンの制御機構と作動様式、Qニューロンに発現する遺伝子の網羅的解析を行う。

Outline of Final Research Achievements

To investigate the mechanisms underlying QIH in detail, we generated the Qrfp-FlpO mouse line and developed the photogenetic tool OPN4ΔC to induce QIH for extended periods (>24 hours). Our findings demonstrated that heart rate changes during QIH induction and recovery phases occur more rapidly than changes in body temperature. Additionally, we conducted mononuclear RNA sequencing of Q neurons to comprehensively identify the genes expressed by these neurons. Our results revealed that agonists of some of these receptors excite Q neurons and that intracerebroventricular administration of these agonists in mice can induce hypothermia.

Academic Significance and Societal Importance of the Research Achievements

神経系の操作による人工冬眠状態であるQIHの生理的状態をよりよく理解するための知見を得たとともに、将来さらに詳細に解明するためのリソースを確立した。また、Qニューロンを興奮させ、低体温を惹起する低分子化合物を開発するために必要な情報を獲得した。

Report

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

    (17 results)

All 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (11 results) (of which Invited: 8 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Optogenetic induction of hibernation-like state with modified human Opsin4 in mice2022

    • Author(s)
      Takahashi Tohru M.、Hirano Arisa、Kanda Takeshi、Saito Viviane M.、Ashitomi Hiroto、Tanaka Kazumasa Z.、Yokoshiki Yasufumi、Masuda Kosaku、Yanagisawa Masashi、Vogt Kaspar E.、Tokuda Takashi、Sakurai Takeshi
    • Journal Title

      Cell Reports Methods

      Volume: 2 Issue: 11 Pages: 100336-100336

    • DOI

      10.1016/j.crmeth.2022.100336

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypothalamic orexin prevents non-alcoholic steatohepatitis and hepatocellular carcinoma in obesity2022

    • Author(s)
      Tsuneki Hiroshi、Maeda Takahiro、Takata Shinjiro、Sugiyama Masanori、Otsuka Koyuki、Ishizuka Hinako、Onogi Yasuhiro、Tokai Emi、Koshida Chiaki、Kon Kanta、Takasaki Ichiro、Hamashima Takeru、Sasahara Masakiyo、Rudich Assaf、Koya Daisuke et al.
    • Journal Title

      Cell Reports

      Volume: 41 Issue: 3 Pages: 111497-111497

    • DOI

      10.1016/j.celrep.2022.111497

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons2022

    • Author(s)
      Islam Md Tarikul、Rumpf Florian、Tsuno Yusuke、Kodani Shota、Sakurai Takeshi、Matsui Ayako、Maejima Takashi、Mieda Michihiro
    • Journal Title

      Current Biology

      Volume: 32 Issue: 18 Pages: 3871-3885

    • DOI

      10.1016/j.cub.2022.07.020

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice2022

    • Author(s)
      Hasegawa Emi、Miyasaka Ai、Sakurai Katsuyasu、Cherasse Yoan、Li Yulong、Sakurai Takeshi
    • Journal Title

      Science

      Volume: 375 Issue: 6584 Pages: 994-1000

    • DOI

      10.1126/science.abl6618

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice2022

    • Author(s)
      Takahashi A, Durand-de Cuttoli R, Flanigan ME, Hasegawa E, Tsunematsu T, Aleyasin H, Cherasse Y, Miya K, Okada T, Keino-Masu K, Mitsui K, Li L, Patel V, Blitzer RD, Lazarus M, Tanaka KF, Yamanaka A, Sakurai T, Ogawa S, Russo SJ
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 4039-4039

    • DOI

      10.1038/s41467-022-31728-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 冬眠様状態における概日振動体の動態と機能2022

    • Author(s)
      平野 有沙、高橋 徹、南部 美友、田中 和正、櫻井 武
    • Organizer
      日本神経科学学会(Neuro2022)沖縄コンベンションセンター
    • Related Report
      2022 Annual Research Report
  • [Presentation] 新規高感度オプシンを用いた冬眠様状態の誘導2022

    • Author(s)
      高橋 徹、平野 有沙、櫻井 武
    • Organizer
      日本神経科学学会(Neuro2022)沖縄コンベンションセンター
    • Related Report
      2022 Annual Research Report
  • [Presentation] 人工冬眠によるてんかん進行の抑制2022

    • Author(s)
      タト ムホトゥ、リン ユジュ、南部 美友、大山 薫、平野 有沙、櫻井 武、田中 和正
    • Organizer
      日本神経科学学会(Neuro2022)沖縄コンベンションセンター
    • Related Report
      2022 Annual Research Report
  • [Presentation] Induction of hypometablic and hypothermic states in mice.2022

    • Author(s)
      Sakurai, T.
    • Organizer
      JST-CREST “Opt Bio”/WPI-IIIS Joint Symposium
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Invited
  • [Presentation] Induction of hibernation-like hypometabolic state by manupulating hypothalamic neurons2022

    • Author(s)
      櫻井 武
    • Organizer
      第99回日本生理学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 冬眠様の制御された低代謝状態を誘導する視床下部神経系2021

    • Author(s)
      櫻井 武
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 冬眠様の制御された低代謝状態を誘導する新規神経回路2021

    • Author(s)
      櫻井 武
    • Organizer
      第28回時間生物学会学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 視床下部神経系の操作による冬眠様の低代謝・低体温状態の誘導2021

    • Author(s)
      櫻井 武
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] マウスにおける冬眠様状態の誘導2021

    • Author(s)
      櫻井 武
    • Organizer
      日本睡眠学会第46回定期学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 冬眠様の制御された低代謝状態を誘導する新規神経回路2021

    • Author(s)
      櫻井 武
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 冬眠様の制御された低代謝状態を誘導する新規神経回路の同定2021

    • Author(s)
      櫻井 武
    • Organizer
      第68回日本実験動物学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 冬眠様状態を誘発する方法およびそのための装置2022

    • Inventor(s)
      櫻井 武、砂川玄志郎、髙橋徹
    • Industrial Property Rights Holder
      櫻井 武、砂川玄志郎、髙橋徹
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report
    • Overseas

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Published: 2021-07-13   Modified: 2024-01-30  

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