Molecula and neral mechanisms of individual- and -sex differences in behavioral resposne to stress
| Project/Area Number |
18H02750
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Uchida Shusaku 京都大学, 医学研究科, 特定准教授 (10403669)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | ストレス / うつ病 / エピゲノム / エピジェネティクス / 個体差 / 性差 / ストレス脆弱性 |
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| 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.
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| 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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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Distinct epigenetic signatures between adult-onset and late-onset depression.2021
Author(s)
Yamagata H, Ogihara H, Matsuo K, Uchida S, Kobayashi A, Seki T, Kobayashi M, Harada K, Chen C, Miyata S, Fukuda M, Mikuni M, Hamamoto Y, Watanabe Y, Nakagawa S
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Journal Title
Scientific Reports
Volume: 27
Pages: 2296-2296
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Characterization of the signature of peripheral innate immunity in women with later-life major depressive disorder2021
Author(s)
Miyata S, Yamagata H, Matsuo K, Uchida S, Harada K, Fujihara K, Yanagawa Y, Watanabe Y, Mikuni M, Nakagawa S, Fukuda M
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Journal Title
Brain, Behavior, and Immunity
Volume: 87
Pages: 831-839
DOI
Related Report
Peer Reviewed
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