Institute of Biomedical Science, Kansai Medical University, Osaka, 573-1010, Japan.
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, 997-0052, Japan.
Commun Biol. 2021 Jan 22;4(1):101. doi: 10.1038/s42003-020-01629-2.
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."
先天恐惧与危机中的生命保护密切相关，尽管这种关系尚未完全被理解。在这里，我们报告称，超正常的先天恐惧诱导剂 2-甲基-2-噻唑啉（2MT）的呈现，而不是学习的恐惧刺激，会引起强烈的全身低温/低代谢，并通过丙酮酸脱氢酶的磷酸化抑制有氧代谢，从而使动物在致命的缺氧环境中得以长期生存。这些反应在皮肤和脑缺血/再灌注损伤模型中发挥了强大的治疗作用。与冬眠不同，2MT 刺激会加速大脑中的葡萄糖摄取，并降低血液中的氧饱和度。全脑映射和化学遗传激活表明，2MT 通过脑干 Sp5/NST 对中脑 PBN 通路的感觉表现来协调生理反应。2MT 作为先天恐惧的超正常刺激，在小鼠中引发了夸张的、潜在的生命保护作用。如果该系统在人类中得以保留，它可能会被用于开创一个新的领域：“感官医学”。
