Artificial hibernation/life-protective state induced by thiazoline-related innate fear odors
Open Access
- 22 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Biology
- Vol. 4 (1), 1-17
- https://doi.org/10.1038/s42003-020-01629-2
Abstract
Innate fear intimately connects to the life preservation in crises, although this relationships is not fully understood. Here, we report that presentation of a supernormal innate fear inducer 2-methyl-2-thiazoline (2MT), but not learned fear stimuli, 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. 2MT, as a supernormal stimulus of innate fear, induced exaggerated, latent life-protective effects in mice. If this system is preserved in humans, it may be utilized to give rise to a new field: “sensory medicine.”Funding Information
- MEXT | Japan Society for the Promotion of Science (20K20578, 18K19350, 18H04806, 16H02591)
- Takeda Science Foundation
- Uehara Memorial Foundation
- Daiichi Sankyo Foundation of Life Science
- Naito Foundation
- Asahi Glass Foundation
- Terumo Foundation for Life Sciences and Arts
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