| Project/Area Number |
17K10278
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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 | Sapporo Medical University |
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Principal Investigator |
HASHIMOTO Eri 札幌医科大学, 医学部, 准教授 (30301401)
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| Co-Investigator(Kenkyū-buntansha) |
山田 美佐 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 科研費研究員 (10384182)
鵜飼 渉 札幌医科大学, 医療人育成センター, 准教授 (40381256)
木川 昌康 札幌医科大学, 医学部, 助教 (50581146)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 神経科学 / 脳・神経 / 精神疾患 / うつ病 / 難治性うつ病モデル / うつ病モデルラット / BDNF / 難治性うつ病 / 神経新生 / 抗うつ薬 |
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| Outline of Final Research Achievements |
We produced depression model rats by exposure of chronic corticosterone treatment and refractory depression model rats by alcohol exposure during the fetal period followed by the corticosterone treatment during adolescent period. The treatment with SSRIs reversed depression-like behavior and normalized BDNF levels in serum and the hippocampus in depression model rats. In contrast, serum BDNF levels were higher in refractory depression model rats than in control rats, and the treatment with escitalopram, but not sertraline reversed depression-like behavior in refractory depression model accompanied by the reduction of BDNF levels in nucleus accumbens. The treatment with blonanserin reversed abnormal social interactions and altered BDNF levels in serum in refractory depression model rats. These results suggest that serum and nucleus accumbens BDNF level reductions have potential in therapeutic interventions for treatment-resistant refractory depression.
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| Academic Significance and Societal Importance of the Research Achievements |
臨床現場においては、標準的な抗うつ薬治療では回復しないうつ病の存在が問題となっており、このような遷延化・難治化するうつ病に対する有用な治療戦略を確立していくことが何よりも求められている。難治性うつ病モデルを用いた本研究により、側坐核でのBDNF変動等の治療的関与が示唆され、報酬系への影響を含め、難治性うつ病の病態理解および新たな治療的アプローチ確立の上での学術的意義および社会的意義は大きい。
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