| Project/Area Number |
16K10183
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Health Sciences University of Hokkaido (2017-2018)
Hokkaido University (2016) |
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Principal Investigator |
IZUMI TAKESHI 北海道医療大学, 薬学部, 教授 (60312360)
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| Research Collaborator |
KOBAYASHI kazuto
NAKAGAWA shin
BOKU shunken
HISHIMOTO akitoyo
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | うつ病 / 扁桃体 / FKBP5 / HPA axis / 動物モデル / うつ病モデル動物 / ストレス / グルココルチコイド / HPA系 / 海馬 / 副腎 / SSRI / 室傍核 / 脳・神経 |
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| Outline of Final Research Achievements |
We investigated the effect of repeated restraint stress (RS) (3 hr/day) on depression-like behaviors using forced swimming test (FST) in rats. Moreover, we assessed the effect of repeated RS on the serum corticosterone by EIA, and on the GR and FKBP5 (inhibitory factor of GR) in the mPFC, hippocampus and amygdala by Western blotting. We performed above these assessments 2 weeks after repeated stress. Seven times RS significantly increased depression-like behavior, and it was antagonized by previous 14 days repeated administration of escitalopram (10 mg/kg), a SSRI. Serum corticosterone was increased by seven times RS. Protein level of GR was not changed, but that of FKBP5 was increased in the amygdala by seven times RS. Hyperactivity of HPA axis and increased FKBP5 in the amygdala may be related to RS-induced depression-like behavior.
Besides, FKBP5 was significantly decreased in the frontal cortex of the suicide completer’s postmortem brain sample compared to normal control.
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| Academic Significance and Societal Importance of the Research Achievements |
複数の多型研究でうつ病との相関が報告されているGR阻害因子FKBP5について、うつ病モデルラットの扁桃体で変化を検出した。FKBP5はカルシニューリンの促進因子でもあり、mTOR系を介してオートファジーを調節するなど、多面的な機能を持つことが報告されている。今後、本研究の結果を手がかりとして、HPA系だけでなく、カルシニューリン系、mTOR系やオートファジーとうつ病との関連へ研究を広げ、将来の新規抗うつ薬の開発につなげていきたい。
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