RRC ID 64295
著者 Matsuo T, Isosaka T, Hayashi Y, Tang L, Doi A, Yasuda A, Hayashi M, Lee CY, Cao L, Kutsuna N, Matsunaga S, Matsuda T, Yao I, Setou M, Kanagawa D, Higasa K, Ikawa M, Liu Q, Kobayakawa R, Kobayakawa K.
タイトル Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation.
ジャーナル Nat Commun
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.
巻・号 12(1)
ページ 2074
公開日 2021-4-6
DOI 10.1038/s41467-021-22205-0
PII 10.1038/s41467-021-22205-0
PMID 33824316
PMC PMC8024280
MeSH Animals Bradycardia / pathology Fear / drug effects Fear / physiology* Gene Expression Regulation / drug effects HEK293 Cells Humans Hypothermia / complications Hypothermia / metabolism* Hypoxia / complications Hypoxia / metabolism* Male Mice, Inbred C57BL Neurons / drug effects Oxygen Consumption / drug effects Sensation / drug effects TRPA1 Cation Channel / metabolism* Thiazoles / chemistry Thiazoles / pharmacology* Time Factors Trigeminal Ganglion / drug effects Trigeminal Ganglion / metabolism Vagus Nerve / drug effects
IF 12.121
リソース情報
ヒト・動物細胞 293(RCB1637)