Pin1 的上调有助于缓解糖尿病小鼠的认知功能障碍。
Upregulation of Pin1 contributes to alleviation of cognitive dysfunction in diabetic mice.
机构信息
Department of Gerontology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Bishan District Traditional Chinese Medical Hospital, Chongqing, China.
出版信息
Brain Behav. 2023 Dec;13(12):e3336. doi: 10.1002/brb3.3336. Epub 2023 Nov 21.
OBJECTIVE
This study aimed to explore the molecular mechanism underlying the role of Pin1 in cognitive dysfunction in diabetic mice.
METHODS
Using a streptozotocin-induced diabetic mouse model, an adeno-associated virus carrying the Pin1 gene was used to upregulate Pin1 expression in the hippocampus of diabetic mice. Animal behavior tests and molecular biology techniques were further used to explore the role of Pin1 in cognitive dysfunction in diabetic mice.
RESULTS
Our study demonstrated that upregulation of Pin1 expression increased the phosphorylation of AKT and insulin receptor substrate 1 downstream signaling molecules of the IR-IGF1R pathway, increased the phosphorylation of GSK-3β, and concomitantly decreased the phosphorylation of Tau in the hippocampus of diabetic mice, thereby improving the ultrastructural pathology of the hippocampus and further alleviating diabetes-related cognitive impairment.
CONCLUSION
Pin1 can improve cognitive dysfunction in diabetic mice.
目的
本研究旨在探讨 Pin1 在糖尿病小鼠认知功能障碍中的作用机制。
方法
采用链脲佐菌素诱导的糖尿病小鼠模型，利用携带 Pin1 基因的腺相关病毒上调糖尿病小鼠海马中的 Pin1 表达。进一步采用动物行为学测试和分子生物学技术，探讨 Pin1 在糖尿病小鼠认知功能障碍中的作用。
结果
我们的研究表明，上调 Pin1 表达可增加 AKT 和胰岛素受体底物 1 的磷酸化，激活胰岛素受体（IR）-胰岛素样生长因子 1 受体（IGF1R）通路的下游信号分子，增加 GSK-3β 的磷酸化，同时降低海马中的 Tau 磷酸化，从而改善海马的超微结构病理学，进一步减轻糖尿病相关的认知障碍。
结论
Pin1 可改善糖尿病小鼠的认知功能障碍。
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