| Project/Area Number |
21H02385
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 42030:Animal life science-related
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| Research Institution | Kansai Medical University |
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Principal Investigator |
Kobayakawa Ko 関西医科大学, 医学部, 教授 (60466802)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 先天的恐怖臭 / 低酸素抵抗性 / Trpa1 / 先天的恐怖 |
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| Outline of Research at the Start |
脳の神経細胞が正常の機能を維持するためにはグルコースや酸素の絶えることのない供給が必要である。病気や外傷などの原因で脳への血液循環が停止すると、短時間で脳神経細胞は不可逆的に破壊されてしまう。私たちは、先天的恐怖臭刺激が特殊な脳神経細胞の状態を誘導し、その結果、致死的な低酸素環境で神経細胞が長時間生存できることを初めて発見した。本研究ではその作用原理を解明し脳を保護する革新的な医療技術を開発する。
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| Outline of Final Research Achievements |
Thiazoline-related innate fear odors (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Here, we show that most of these effects are severely attenuated in transient receptor potential ankyrin 1 (Trpa1) knockout mice. TFO-induced hypothermia involves the Trpa1-mediated trigeminal/vagal pathways and non-Trpa1 olfactory pathway. TFOs activate Trpa1-positive sensory pathways projecting from trigeminal and vagal ganglia to the spinal trigeminal nucleus (Sp5) and nucleus of the solitary tract (NTS), and their artificial activation induces hypothermia. TFO presentation activates the NTS-Parabrachial nucleus pathway to induce hypothermia and hypometabolism. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. Accordingly, we find a novel molecule that enables mice to survive in a lethal hypoxic condition ten times longer than known tFOs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、tFOが低体温、低代謝、低酸素抵抗性などの保護的生理応答を誘発するメカニズムが明らかになるとともに、メカニズムを研究する過程で極めて強力な低酸素抵抗性を誘導する新規分子を発見し、低酸素関連疾患に対する新たな治療法の可能性を拓いた。
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