Principles and technical applications of odor-induced artificial hibernation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K20578
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: Kansai Medical University
• Principal Investigator: KOBAYAKAWA Ko 関西医科大学, 医学部, 准教授 (60466802)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 先天的恐怖 / 感覚刺激性冬眠 / 人工冬眠・生命保護状態 / 感覚創薬 / チアゾリン類恐怖臭 / TRPA1 / 虚血再灌流障害 / 敗血症

Outline of Final Research Achievements

We found that thiazoline fear odor (tFO)-stimulation induces an artificial hibernation and life-protective state accompanied by hypothermia and hypometabolism and allows long-term survival in lethal hypoxic and inflammatory conditions. This effect was strongly suppressed in knockout mice of the tFO receptor TRPA1. TFO-stimulation induced protective effects via activation of the brainstem-midbrain pathway. Importantly, induction of protective effects required not only agonist of TRPA1, but also activation of the brainstem-midbrain pathway. Following this principle, we discovered a novel TRPA1 agonist odor molecule that induces extremely potent hypoxic resistance. Furthermore, we demonstrated the therapeutic effects of tFO-stimulation in models of ischemia-reperfusion injury and hypoxic injury.

Free Research Field

感覚創薬

Academic Significance and Societal Importance of the Research Achievements

本研究などで、先天的恐怖情動を誘導する活性を持つチアゾリン類恐怖臭刺激が、人工冬眠・生命保護状態と名付けた、低体温・低代謝を基盤とし、低酸素耐性や抗炎症作用を伴う、危機状態での生存確率を上昇させる特殊な生理状態を誘導するという予想外の新生命現象が発見された。さらに、この状態の誘導が三叉・迷走神経のTRPA1受容体が適切な種類のアゴニスト匂い分子により誘導されることを始めとした、分子や神経回路レベルでの作用機序も解明された。生物が持つ潜在的な保護能力を匂い分子刺激で誘導し疾患を治療する感覚創薬という革新的な医療技術への応用が切り開かれた。生存は生物の根源目的であり、それへ迫る新概念を確立した。