Project/Area Number |
17K11068
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Anesthesiology
|
Research Institution | University of Tsukuba |
Principal Investigator |
|
Project Period (FY) |
2017-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 術後認知機能障害 / 高齢 / グリコーゲン合成酵素キナーゼ3 / 海馬 / 樹状突起 / Morris water maze / 術後高次機能障害 / グリコーゲン合成酵素キナーゼ3β阻害薬 / グリコーゲン合成酵素キナーゼ3 / 認知機能障害 / 手術 / GSK-3β |
Outline of Final Research Achievements |
This study was conducted to evaluate the effect of preoperative 5 ㎎/kg of Tideglusib, which was a GSK-3β inhibitor, on the postoperative cognitive dysfunction in aged rats, and investigate whether the the GSK-3β levels and neuronal dendritic spine morphological changes in the hippocampus was related with the effect of preoperative Tideglusib. We found that Tideglusib had a protective effect on the postoperative cognitive dysfunction, which was thought to be related to the inhibition of increased GSK-3β activity and neuronal dendritic spine morphological changes in the hippocampus. On the other hand, administration of Tideglusib to normal rats caused neuropsychiatric abnormalities, and the application of GSK-3β inhibitors against the postoperative cognitive dysfunction may require further study.
|
Academic Significance and Societal Importance of the Research Achievements |
術後の認知機能障害は高齢患者に特有の周術期合併症であり、今後ますます高齢化社会を迎える我が国にとってその予防は重大なテーマの一つである。Tideglusibはアルツハイマー病の臨床開発においてすでに臨床試験が行われたGSK-3β阻害薬である。今回、Tideglusibに術後の認知機能障害への効果が明らかになったことで、今後の臨床応用が期待される。一方で、Tideglusibを投与した正常なラットに精神神経学的な異常が認められており、GSK-3β阻害薬の術後認知機能障害への応用のために解決が必要な課題が提示できたと考える。
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