Development of novel therapeutic approaches focused on phosphodiesterases for psychiatric disorders
| Project/Area Number |
16K10198
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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 | Kurume University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西 昭徳 久留米大学, 医学部, 教授 (50228144)
首藤 隆秀 久留米大学, 医学部, 講師 (70412541)
大西 克典 久留米大学, 医学部, 助教 (10626865)
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| Research Collaborator |
Hikida Takatoshi
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ホスホジエステラーゼ / ドーパミン / うつ病 / 海馬歯状回 / 統合失調症 / 脳神経疾患 / 脳・神経 / 薬理学 |
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| Outline of Final Research Achievements |
Depression is one of the most common psychiatric disorders, but the etiology of depression is not fully understood. To address the role of adolescent stress in the development of depression, we combined a transgenic mouse model in which a mutation of DISC1, used as a genetic risk factor and adolescent social isolation stress. Both DISC1-mutant mice and wild-type mice with social isolation stress showed depression-like behaviors and showed modest differences in dopamine D1 receptor signaling in the prefrontal cortex and hippocampal dentate gyrus. In addition, in the wild-type mice with environmental enrichment showed enhanced effects of the PDE4 inhibitor rolipram on PKA signaling in the dentate gyrus, however, wild-type mice with social isolation stress showed attenuation of the effects of rolipram. These results suggest that the mutation of DISC1 and social isolation stress may contribute to the development of depression.
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| Academic Significance and Societal Importance of the Research Achievements |
個別飼育ストレスを負荷したDISC1遺伝子改変マウスは、遺伝因子と思春期の環境因子の相乗作用が発症要因であるとするtwo-hit-theory に合致した有用な動物モデルである。
本研究の結果より、うつ病の発症には遺伝的素因とストレスの負荷が関与していることが示唆され、うつ病のメカニズム解明の糸口となることが期待される。また、うつ病モデル動物を用いた研究およびストレス負荷を行う研究においては、対照群を含め、環境エンリッチメントを始めとする飼育環境の条件設定を厳密に行う必要があることが明らかとなった。
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Report
(4 results)
Research Products
(7 results)
