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

Commun Biol. 2021 Jan 22;4(1):101. doi: 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."

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Fear / physiology*
  • Hibernation*
  • Hypothermia, Induced
  • Hypoxia
  • Instinct*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Odorants*
  • Reperfusion Injury / prevention & control
  • Thiazoles*

Substances

  • Thiazoles
  • 2-methylthiazoline