Artificial hibernation/life-protective state induced by thiazoline-related innate fear odors

Author:

Matsuo Tomohiko,Isosaka Tomoko,Tang Lijun,Soga Tomoyoshi,Kobayakawa Reiko,Kobayakawa KoORCID

Abstract

AbstractInnate 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.”

Funder

MEXT | Japan Society for the Promotion of Science

Takeda Science Foundation

Uehara Memorial Foundation

Daiichi Sankyo Foundation of Life Science

Naito Foundation

Asahi Glass Foundation

Terumo Foundation for Life Sciences and Arts

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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