Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation
Year: 2021
Type: article
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.
Source: Nature Communications
Authors: 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, Ko Kobayakawa
Institutions: Kansai Medical University, University of Tsukuba, International Institute for Integrative Sleep Medicine, University of Tsukuba, The University of Tokyo, Tokyo University of Science, Hamamatsu University, Hamamatsu University School of Medicine, Research Institute for Microbial Diseases, The University of Osaka, The University of Osaka, National Institute of Biological Sciences, Beijing
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: Canon Foundation in Europe, Naito Foundation, Takeda Science Foundation, Asahi Glass Foundation, Sumitomo Foundation, Uehara Memorial Foundation, Ministry of Education, Culture, Sports, Science and Technology, Daiichi Sankyo Foundation of Life Science, Terumo Foundation for Life Sciences and Arts, Mishima Kaiun Memorial Foundation, Japan Society for the Promotion of Science, Japan Science and Technology Agency
Awards: G174089439, G1780106009, Neural dynamics and memory consolidation in prefrontal cortex, Innate fear odor orchestrate survival fate in mice, Regulation of cognitive function by neuron- and glia-derived exosomes in Alzheimer's disease model mice, G305721583, Sensory receptor genes regulating odor-induced fearful behaviors, G3538618486, Elucidation of the mechanisms controlling innate fear-induced hypothermia, Neural circuits involved in fear-induced physiological responess, G5367212563, Principles and technical applications of odor-induced artificial hibernation, G5666452742, Imaging analyses of chromatin dynamics in plant regeneration, Analysis of olfactory receptors in odorant-induced physiological reponses, Elucidate the neural mechanisms underlying sleep disturbances in neurodevelopmental disorders-focusing on CDKL5 deficiency disorder-, Elucidation of the Pathogenesis of Hereditary Diseases through the Development of Ultra-Precision Personalized Genome Analysis Methods, G6913746294, Elucidation of life-protective effects induced by innate fear odor, G7362241833, Molecular mechanisms linking emotion and body temperature
OpenAlex ID: W3141165866