Physiological functions in stress response and cognitive function of Neuromedin U system

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08522
• 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: Oita University
• Principal Investigator: Hanada Reiko 大分大学, 医学部, 教授 (00343707)
• Co-Investigator(Kenkyū-buntansha): 花田 俊勝 大分大学, 医学部, 教授 (10363350) ; 疋田 貴俊 大阪大学, 蛋白質研究所, 教授 (70421378)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 神経ペプチド / ストレス / 脳内高次機能 / 遺伝子改変マウス / 予期不安

Outline of Final Research Achievements

Neuromedin U (NMU) and neuromedin S(NMS) are neuronal peptides with multiple physiological functions. There are several reports that the NMU/NMS system is related with higher brain functions. Focusing on stress and cognitive function, we have established NMU/NMS gene-deficient mice (NMU/NMS dKO mice) and performed a series of behavioral experiments. Passive avoidance tests observed marked enhancement, retention of fear memory at 1, 7, and 28 days after stress treatment. NMU / NMS dKO mice showed a significant increase in the number of c-Fos positive neuronal cells in the hippocampus and amygdala at 28days after stress treatment. We are currently examining a series of neurotransmitter and molecular dynamics, focusing on the brain regions where differences were observed in c-Fos experiment. Based on these evidences, we are elucidating the detailed molecular mechanism of these phenomena of the NMU/NMS system in the brain.

Free Research Field

内分泌学、生理学

Academic Significance and Societal Importance of the Research Achievements

過度のストレスは生体の恒常性を破綻し、脳内においては神経細胞にダメージを与えて認知機能の低下を招く。本研究では、生理活性ペプチド・ニューロメジンU（NMU）ならびにニューロメジンS（NMS）両遺伝子欠損マウスを用いた実験から、脳内NMUシステムがストレス応答や認知機能に関与することが明らかとなった。本研究で見出された成果をもとに、脳内NMUシステムの新たな生理機能やその分子機構の解明が期待される。また、NMU、NMSは内因性ペプチドであるため、精神・神経疾患を含む難治性疾患の診断や治療法開発へつながる可能性も期待される。