Elucidation of life-protective effects induced by innate fear odor

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02546
• 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): 2018-04-01 – 2021-03-31
• Keywords: 先天的恐怖 / 生命保護作用

Outline of Final Research Achievements

Innate fear intimately connects to the life preservation in crises, although this relationships is not fully understood. Here, we elucidated 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

本研究により、先天的恐怖を誘発する超正常刺激である2MTは、マウスにおいて非常に強力な潜在的な生命保護効果を誘発し、複数の疾患モデルにおいて治療効果を持つことが明らかになった。このシステムがヒトにも保存されていれば、匂いによって潜在的な生命保護作用を引き起こす「感覚創薬」という全く新しい創薬が可能になると考えられる。