| Project/Area Number |
18K06687
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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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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大河原 雄一 東北医科薬科大学, 薬学部, 教授 (40333801)
小野木 弘志 東北福祉大学, 健康科学部, 准教授 (50610200)
根本 亙 東北医科薬科大学, 薬学部, 助教 (80635136)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | アンジオテンシン / うつ病 / 神経新生 / カプトプリル / Ang(1-7) / BDNF / Mas受容体 / アンジオテンシン系 / Ang (1-7) |
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| Outline of Final Research Achievements |
Olfactory bulbectomized (OBX) mice shows neurochemical and behavioral changes similar to those observed in individuals with depressive disorders. Intraperitoneal administration of Captopril (CAP) for one week showed antidepressant-like effects in OBX mice. Previous study revealed that CAP treatment increased angiotensin (1-7) [Ang (1-7)] levels in rat brain. OBX mice showed reduced hippocampal Ang (1-7), Brain-derived neurotrophic factor (BDNF) levels and neurogenesis. Interestingly, these changes were reversed by CAP administration. Further, antidepressant-like effect of CAP was abolished by the co-administration of an antagonist for Ang (1-7) receptor MAS. These results suggest that CAP-induced antidepressant-like effects may be associated with enhanced hippocampal neurogenesis via Ang (1-7) / MAS signaling pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで血圧などの循環器系にAngiotensin (Ang)系が関与していることが分かっていたが、今回の研究により脳内のAng系がうつ病にも関与するという新たな機能的役割を見出した。さらに、うつ病動物モデルに対し高血圧の治療に用いられている既存のAng変換酵素阻害薬（ACE阻害薬）であるカプトプリル（一般名）が抗うつ作用を有することを発見した。これらのことから、ACE阻害薬は循環器系疾患のみならず、既存の抗うつ薬よりも副作用が軽度な抗うつ薬として新規適応拡大（エコファーマ）の可能性が期待される。
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