Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation

Tomohiko Matsuo, Tomoko Isosaka, Yuichiro Hayashi, Lijun Tang, Akihiro Doi, Aiko Yasuda, Mikio Hayashi, Chia-Ying Lee, Liqin Cao, Natsumaro Kutsuna, Sachihiro Matsunaga, Takeshi Matsuda, Ikuko Yao, Mitsuyoshi Setou, Dai Kanagawa, Koichiro Higasa, Masahito Ikawa, Qinghua Liu (), Reiko Kobayakawa () and Ko Kobayakawa ()
Additional contact information
Tomohiko Matsuo: Kansai Medical University
Tomoko Isosaka: Kansai Medical University
Yuichiro Hayashi: Kansai Medical University
Lijun Tang: Kansai Medical University
Akihiro Doi: Kansai Medical University
Aiko Yasuda: Kansai Medical University
Mikio Hayashi: Kansai Medical University
Chia-Ying Lee: University of Tsukuba
Liqin Cao: University of Tsukuba
Natsumaro Kutsuna: University of Tokyo
Sachihiro Matsunaga: Tokyo University of Science
Takeshi Matsuda: Hamamatsu University School of Medicine
Ikuko Yao: Hamamatsu University School of Medicine
Mitsuyoshi Setou: Hamamatsu University School of Medicine
Dai Kanagawa: Kansai Medical University
Koichiro Higasa: Kansai Medical University
Masahito Ikawa: Osaka University
Qinghua Liu: University of Tsukuba
Reiko Kobayakawa: Kansai Medical University
Ko Kobayakawa: Kansai Medical University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Thiazoline-related innate fear-eliciting compounds (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; this activation was suppressed in Trpa1 knockout mice. 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. Combinations of appropriate tFOs and TRPA1 command intrinsic physiological responses relevant to survival fate.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22205-0

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DOI: 10.1038/s41467-021-22205-0

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