Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation
| Autor: | Yuichiro Hayashi, Sachihiro Matsunaga, Mikio Hayashi, Tomoko Isosaka, Lijun Tang, Mitsuyoshi Setou, Dai Kanagawa, Tomohiko Matsuo, Reiko Kobayakawa, Chia-Ying Lee, Aiko Yasuda, Qinghua Liu, Liqin Cao, Koichiro Higasa, Ikuko Yao, Natsumaro Kutsuna, Takeshi Matsuda, Ko Kobayakawa, Masahito Ikawa, Akihiro Doi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Olfactory system Male Time Factors Physiology Science Sensation General Physics and Astronomy Sensory system Hypothermia General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine Oxygen Consumption medicine Bradycardia Animals Humans Hypoxia TRPA1 Cation Channel Neurons Multidisciplinary Chemistry Spinal trigeminal nucleus Solitary tract food and beverages Vagus Nerve General Chemistry Fear Hypoxia (medical) Mice Inbred C57BL Thiazoles 030104 developmental biology medicine.anatomical_structure HEK293 Cells Gene Expression Regulation Trigeminal Ganglion Knockout mouse medicine.symptom Neuroscience 030217 neurology & neurosurgery psychological phenomena and processes |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2041-1723 |
| Popis: | 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. Matsuo et al. report that thiazoline-related innate fear-eliciting compounds activate the spinal trigeminal nucleus (Sp5) and the nucleus of the solitary tract (NTS) via vagal/trigeminal TRPA1 to induce robust physiological alterations, enabling long time survival in a lethal hypoxic environment. |
| Databáze: | OpenAIRE |
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