Elucidation of the pathogenesis of stress-related psychiatric disorders based on the GAPDH cascade and development of treatment strategies
| Project/Area Number |
16H05029
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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 |
Veterinary medical science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
桑村 充 大阪府立大学, 生命環境科学研究科, 准教授 (20244668)
乾 隆 大阪府立大学, 生命環境科学研究科, 教授 (80352912)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | ストレス性精神疾患 / 遺伝子ノックダウン / GAPDH / 阻害剤 / 抗うつ薬 / 抗不安薬 / 抗ストレス薬 / 行動実験 / 獣医薬理 / 創薬 / 行動薬理 / 治療薬 / ストレス / 精神疾患 / 酸化ストレス / うつ・不安様行動 / GAPDH核移行 / 脳内酸化ストレス / 社会性ストレス / 海馬神経新生 |
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| Outline of Final Research Achievements |
Using mouse chronic stress models and acute stress models, it was found that the nuclear translocation cascade of glycolysis enzyme GAPDH is activated in the hippocampus, which is deeply involved in stress-related psychiatric disorders. In addition, by the hippocampal GAPDH gene knockdown method, it was clarified that the hippocampal GAPDH expression level correlated with the increase in adrenal weight, which is an indicator of mouse depressive anxiety behavior and stress response, and the amount of corticosterone in the blood. Furthermore, we clarified that oral administration of the GAPDH nuclear transition inhibitor CGP3466B exhibits antidepressant, anxiety, and anti-stress effects by a mechanism different from the pre-existing antidepressant clomipramine.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、ストレス性精神疾患において、脳内酸化ストレスに起因するGAPDHの核移行は、その病態形成に関与する重要な機序であり、その特異的阻害剤は、従来の抗うつ薬とは作用機序が異なり、生体ストレス反応に重要なHPA軸を標的とし、副作用が少なく治療効果発現もクイックな新規ストレス性精神疾患治療薬となる可能性が示された。
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Report
(5 results)
Research Products
(16 results)
