コバヤカワ　コウ   KOBAYAKAWA KOU   小早川　高    所属   関西医科大学  附属生命医学研究所侵襲反応制御部門    職種   研究所教授
言語種別	英語
発表タイトル	Artificial hibernation/life-protective state induced by thiazoline-related innate fear odors via sensory TRPA1 activation
会議名	第44回　日本神経科学大会
主催者	日本神経科学学会
学会区分	国際学会及び海外の学会
発表形式	口頭
講演区分	一般
発表者・共同発表者	◎Ko　Kobayakawa
発表年月日	2021/07/30
開催地 （都市, 国名）	神戸
概要	Innate fear intimately connects to the life preservation in crises, although this relationship is not fully understood. Here, we report that presentation of a supernormal innate fear inducer 2-methyl-2-thiazoline (2MT) induced robust systemic hypothermia/hypometabolism and suppressed aerobic metabolism via phosphorylation of pyruvate dehydrogenase, thereby enabling long-term survival in a lethal hypoxic environment. These responses exerted potent therapeutic effects in cutaneous and cerebral ischemia/reperfusion injury models. In contrast to hibernation, 2MT stimulation accelerated glucose uptake in the brain and suppressed oxygen saturation in the blood. Whole-brain mapping and chemogenetic activation revealed that the sensory representation of 2MT orchestrates physiological responses via brain stem Sp5/NST to midbrain PBN pathway. Thiazoline-related innate fear-eliciting compounds (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Most of these effects are severely attenuated in 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. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. 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. If this system is preserved in humans, it may be utilized to give rise to a new field: “sensory medicine.