TY - JOUR
T1 - Artificial hibernation/life-protective state induced by thiazoline-related innate fear odors
AU - Matsuo, Tomohiko
AU - Isosaka, Tomoko
AU - Tang, Lijun
AU - Soga, Tomoyoshi
AU - Kobayakawa, Reiko
AU - Kobayakawa, Ko
N1 - Funding Information:
We are grateful to Dr. Kiichi Hirota for providing suggestions regarding the analysis of anti-hypoxia effects. We are grateful to Drs. Shigetada Nakanishi and Tatsuo Kinashi for critical comments on the manuscript. We thank Dai Kanagawa and Aiko Yasuda for providing technical assistance. This work was supported by the following foundations: JSPS KAKENHI (16K07445 to T.M.; 16H06142 to T.I.; 20H04849, 18H02546, 17H05586, and 16K14558 to R.K.; 20K20578, 18K19350, and 18H04806, 16H02591 to K.K.); the Japan Science and Technology Agency, A-STEP grant (to R.K.); the Takeda Science Foundation (to T.M., T.I., R.K. and K.K.); the Canon Foundation (to K.K.); the Dai-ichi Sankyo Foundation (to R.K. and K.K.); the Naito Foundation (to T.I. and K.K.); the Sumitomo Foundation (to K.K.); the Uehara Foundation (to K.K.); the Asahi Glass Foundation (to K.K.); the Terumo Foundation (to K.K.); Mishima Kaiun Memorial Foundation (to T.M.); and AMED-CREST (JP18gm010003 (to T.S.).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.”
AB - 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.”
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U2 - 10.1038/s42003-020-01629-2
DO - 10.1038/s42003-020-01629-2
M3 - Article
C2 - 33483561
AN - SCOPUS:85099969665
SN - 2399-3642
VL - 4
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 101
ER -