Roles and mechanisms of stress-induced functional and structural alterations of prefrontal cortex
| Project/Area Number |
16H05132
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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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| Research Field |
General pharmacology
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北岡 志保 神戸大学, 医学研究科, 助教 (00545246)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 薬理学 / 神経科学 / ストレス / うつ病 / 前頭前皮質 |
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| Outline of Final Research Achievements |
Social stress often induces emotional alterations such as depression, and can be a risk factor for mental illness. However, the mechanism remains elusive. Using a mouse model of social defeat stress, here we found that single stress exposure induces dendritic hypertrophy of prefrontal neurons associated with stress resilience through dopamine D1 receptor, whereas repeated stress exposure activates prefrontal microglia through innate immune receptors TLR2/4 and consequently leads to dendritic atrophy of prefrontal neurons and depression-like behavior.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果は、単回ストレスと反復ストレスの作用の違いを神経細胞の形態的可塑性に着目して明らかにし、さらにストレスによる情動変容にミクログリア活性化を中心とする脳内炎症反応が重要であることを世界に先駆けて立証した。この成果はストレスの生物学的基盤について概念的な進歩を与えるとともに、ストレスの各作用を選択的に制御することが精神疾患創薬に不可欠であること、ミクログリアや炎症関連分子が精神疾患の新たな標的となることを提唱するもので、社会的意義は大きい。
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Report
(4 results)
Research Products
(75 results)
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[Journal Article] Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice2017
Author(s)
Shinohara R, Taniguchi M, Ehrlich AT, Yokogawa K, Deguchi Y, Cherasse Y, Lazarus M, Urade Y, Ogawa A, Kitaoka S, Sawa A, Narumiya S, *Furuyashiki T.
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Journal Title
Mol Psychiatry
Volume: -
Issue: 8
Pages: 1717-1730
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Depressive-like behaviors are regulated by NOX1/NADPH oxidase by redox modification of NMDA receptor 1.2017
Author(s)
Ibi M, Liu J, Arakawa N, Kitaoka S, Kawaji A, Matsuda KI, Iwata K, Matsumoto M, Katsuyama M, Zhu K, Teramukai S, Furuyashiki T, Yabe-Nishimura C.
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Journal Title
J Neurosci
Volume: 37
Issue: 15
Pages: 4200-4212
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] G-CSF-induced sympathetic tone provokes fever and primes antimobilizing functions of neutrophils via PGE2.2017
Author(s)
Kawano Y, Fukui C, Shinohara M, Wakahashi K, Ishii S, Suzuki T, Sato M, Asada N, Kawano H, Minagawa K, Sada A, Furuyashiki T, Uematsu S, Akira S, Uede T, Narumiya S, Matsui T, Katayama Y.
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Journal Title
Blood
Volume: 129
Issue: 5
Pages: 587-597
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] mDia and ROCK mediate actin-dependent presynaptic remodeling regulating synaptic efficacy and anxiety.2016
Author(s)
Deguchi Y, Harada M, Shinohara R, Lazarus M, Cherasse Y, Urade Y, Yamada D, Sekiguchi M, Watanabe D, Furuyashiki T, Narumiya S.
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Journal Title
Cell Reports
Volume: 17
Issue: 9
Pages: 2405-2417
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] ストレスと脳内炎症様変化2016
Author(s)
古屋敷 智之
Organizer
第36回鎮痛薬・オピオイドペプチドシンポジウム
Place of Presentation
北海道大学（北海道札幌市）
Year and Date
2016-08-19
Related Report
Invited
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