Identification of neural circuits for induction of torpor and induction of artificial hibernation

• Project/Area Number: 19K22465
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Sakurai Takeshi 筑波大学, 医学医療系, 教授 (60251055)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 休眠 / 冬眠 / 視床下部 / 体温調節 / 視索前野 / 体温制御 / 低代謝 / 体温 / 人工冬眠

Outline of Research at the Start

応募者らが新たに見出した、脳内の視床下部に局在する神経細胞群は、人工的に興奮させるとマウスを冬眠様の状態にすることが可能である。その神経回路網や、低体温、低代謝を誘導するメカニズムを明らかにし、将来的に冬眠状態を医療に応用するための技術を開発する基礎的なデータを得る。

Outline of Final Research Achievements

When a population of about 800 neurons expressing the neuropeptide Qrfp gene in the anterior ventral periventricular nucleus (AVPe) of the mouse hypothalamus was specifically excited, body temperature dropped significantly to near ambient temperature for several days, and metabolism also decreased significantly. In many respects, this state closely resembles hibernation seen in hibernating animals.

Academic Significance and Societal Importance of the Research Achievements

非冬眠動物に冬眠様状態を誘導できることを示したこの発見は体温制御・代謝制御の新たな機構の発見という生物学的に大きな意義をもつものである。また、今後Ｑニューロンに発現する遺伝子の網羅的解明に伴い、その活動を制御しうる薬物などの開発に資するものである。このような薬物などにより、Ｑニューロン活動を人為的に操作させる技術が開発された場合、ヒトの人工冬眠が現実味を帯びてくることを示した。

Research Products

• [Journal Article] A discrete neuronal circuit induces a hibernation-like state in rodents (2020)
  • Author(s): Takahashi TM, Sunagawa GA, Soya S, Abe M, Sakurai K, Ishikawa K, Yanagisawa M, Hama H, Hasegawa E, Miyawaki A, Sakimura K, Takahashi M, Sakurai T.
  • Journal Title: Nature Volume: - Issue: 7814 Pages: 109-114
  • DOI: 10.1038/s41586-020-2163-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A novel neuronal circuit that induces hibernation-like state in rodents. (2021)
  • Author(s): Takeshi Sakurai
  • Organizer: The 7th Neuroscience Network, Diversity of Brain Science Feb 10th 2021, Online
  • Int'l Joint Research / Invited
• [Presentation] A neuronal circuit that induces regulated hypometabolism in mice (2020)
  • Author(s): Takeshi Sakurai
  • Organizer: Virtual 8th International Conference on the Physiology and Pharmacology of Temperature Regulation (vPPTR 2020) October 26-29, 2020 North Vancouver, BC Canada
  • Int'l Joint Research / Invited
• [Presentation] Induction of Hibernation-like state in mice. (2019)
  • Author(s): Takeshi Sakurai
  • Organizer: 2019第５回国際神経ペプチド学会日本支部シンポ
  • Int'l Joint Research / 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 (2020)
  • 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: 2020
  • Overseas
• [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 (2019)
  • Inventor(s): 櫻井武、高橋徹、砂川玄志郎
  • Industrial Property Rights Holder: 櫻井武、高橋徹、砂川玄志郎
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019