The llife-protective effects of innate fear emotions.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02599
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Kansai Medical University
• Principal Investigator: KOBAYAKAWA Reiko 関西医科大学, 医学部, 教授 (40372411)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 先天的恐怖 / 生命保護

Outline of Final Research Achievements

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.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

冬眠とは対照的に、TFO刺激は脳内のグルコース取り込みを促進し、血液中の酸素飽和度を抑制した。全脳マッピングと化学遺伝学的活性化により、TFOの感覚表現が脳幹Sp5/NSTから中脳PBN経路を介して生理的反応を制御していることが明らかになった。TFOは、先天的恐怖の超正常刺激として、マウスに強力な潜在的な生命保護作用を誘導することから新たな治療法のシーズとなる可能性がある。