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2020 Fiscal Year Final Research Report

Molecula and neral mechanisms of individual- and -sex differences in behavioral resposne to stress

Research Project

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Project/Area Number 18H02750
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionKyoto University

Principal Investigator

Uchida Shusaku  京都大学, 医学研究科, 特定准教授 (10403669)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywordsストレス / うつ病 / エピゲノム
Outline of Final Research Achievements

This study aimed to clarify the molecular mechanism of individual difference in stress adaptation. To this end, we performed a comprehensive gene expression analysis with stress-susceptible and -resilient mice and in clinical depression. We found increased KDM5C expression in depressed individual and stress-susceptible mice. We generated transgenic mice overexpressing KDM5C and found that these TgM has stress-vulnerability. Conversely, KDM5C knockout mice showed stress resilient phenotypes. We also identified two genes as KDM5C target genes, which are also involved in behavioral response to stress. These data suggest that KDM5C-mediated epigenetic gene expression could be involved in behavioral response to stress.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

ストレスによる脳機能低下の個体差構築のメカニズム解明は、うつ病などのストレス性精神疾患の予防・治療法の確立につながることが期待される。本研究は、うつ病発症に関わるとされるストレス脆弱性の個体差構築にはエピジェネティックな遺伝子発現制御異常に起因する神経ネットワーク変容が関わるとの仮説を検証することを目的とした。その成果として、KDM5Cを介したエピジェネティックな遺伝子発現がストレス反応の個体差・性差構築に関わっていることが示唆され、KDM5Cを標的とした薬剤の抗ストレス・抗うつ作用が期待される。

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Published: 2022-01-27  

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