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

Author

Listed:
  • 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
    LPixel Inc.)

  • 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
    National Institute of Biological Sciences)

  • Reiko Kobayakawa

    (Kansai Medical University)

  • Ko Kobayakawa

    (Kansai Medical University)

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.

Suggested Citation

  • 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 & I, 2021. "Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22205-0
    DOI: 10.1038/s41467-021-22205-0
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