Elucidation of physiological significance of newly discovered CRH release pathway and its relationship with known HPA axis

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04025
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: FUKUDA Atsuo 浜松医科大学, 医学部, 教授 (50254272)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 摂食 / 室傍核 / AgRP / CRH / 弓状核 / 正中隆起 / GABA / NKCC1

Outline of Final Research Achievements

The identification and physiological significance of the cell subtypes of the novel CRH release pathway were clarified using AgRP cell-selective (arcuate nucleus) and CRH cell-selective (paraventricular nucleus) genetically modified mice. Blood corticosterone levels were measured in undernutrition stress model and the difference from pharmacogenetic stimulation of AgRP cells was evaluated. As a result, pharmacogenetic stimulation of the entire AgRP cells activated CRH cells in the paraventricular nucleus. Undernutrition also activated a part of AgRP cells but not CRH cells. Serum corticosterone increased in both cases. From the above, we elucidated the mechanism by which a part of AgRP cell population in the arcuate nucleus respond to malnutrition, which increases the activity of the novel HPA axis at median eminence and causes CRH secretion.

Free Research Field

神経生理学、発達神経科学、ストレス、神経内分泌

Academic Significance and Societal Importance of the Research Achievements

GABAはCRH 細胞の反応を室傍核（細胞体）で抑制、正中隆起（軸索終末）で促進し、相反的にCRH 放出を制御すると考えられている (Kakizawa, Sci Adv 2016)。今回我々は弓状核のAgRP陽性GABA 細胞のうち一部の集団のみが低栄養に反応して正中隆起からのCRH放出を起こすことを突き止めた（低栄養による新規HPA 軸選択的活性化）。すなわち、肉体的・精神的ストレスでの既知HPA軸の活性化とは異なる経路を介して、低栄養状態に対してストレス応答することを見出したことは学術的・社会的に意義がある。