Identification of CRF neuronal circuitry in the brain using CRFR1-Cre and CRFR2-Cre mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08563
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tohoku Fukushi University
• Principal Investigator: Itoi Keiichi 東北福祉大学, 健康科学部, 教授 (60232427)
• Co-Investigator(Kenkyū-buntansha): 松井 広 東北大学, 生命科学研究科, 教授 (20435530)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 遺伝子改変マウス / 脳 / ウイルスベクター / 行動 / 摂食

Outline of Final Research Achievements

A Cre-dependent GFP-expressing reporter mouse was crossed with either the CRFR1-Cre knock-in mouse or the CRFR2-Cre knock-in mouse, and it was verified that the distribution of GFP-expressing neurons in the brain recapitulated that of either CRFR1-expressing neurons or CRFR2-expressing neurons that were reported previously. Therefore, Cre recombination took place in accordance with the CRFR1 gene- and CRFR2 gene expression, respectively. Then, CRFR1-Cre and CRFR2-Cre were crossed with either the Cre-dependent ChR2-expressing- or the Cre-dependent ACR2-expressing mouse. ChR2 or ACR2 was excited by blue light via optic fibers implanted into discrete brain regions. Thus, CRFR1-expressing neurons or CRFR2-expressing neurons were stimulated or suppressed in separate brain regions. Anxiety-like behaviors, depression-like behaviors, or the effect on eating behavior was monitored and compared with those of control mice without light exposure.

Free Research Field

神経内分泌学

Academic Significance and Societal Importance of the Research Achievements

視床下部室傍核（PVH）のCRFニューロンは視床下部－下垂体－副腎系の中枢であるが， CRFニューロンは正中隆起以外にも広範な脳内領域に投射し，PVH内で亜核を形成している．本研究ではCRFR1およびCRFR2発現ニューロンを脳内部位別に刺激または抑制し，PVH CRFニューロンが不安様行動うつ様行動，および摂食に関与する脳内神経路を明らかにした．気分障害や神経性食思不振症などはストレスが発症・増悪因子であることから本研究の成果は将来ストレス関連疾患の新たな治療法・予防法の開発に寄与することができる．