Principle of induction of the ability to survive in lethal hypoxic conditions by innate fear odour.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02385
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: Kansai Medical University
• Principal Investigator: Kobayakawa Ko 関西医科大学, 医学部, 教授 (60466802)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 先天的恐怖臭 / 低酸素抵抗性 / Trpa1

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.

Free Research Field

神経科学

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。