cPKCγ Deficiency Exacerbates Autophagy Impairment and Hyperphosphorylated Tau Buildup through the AMPK/mTOR Pathway in Mice with Type 1 Diabetes Mellitus  

作　　者：Jiayin Zheng Yue Wang Yue Liu Song Han Ying Zhang Yanlin Luo Yi Yan Junfa Li Li Zhao 

机构地区：[1]Department of Neurobiology and Center of Stroke,Beijing Institute for Brain Disorders,Capital Medical University,Beijing,100069,China [2]The National Clinical Research Center for Mental Disorders&Beijing Key Laboratory of Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,100088,China [3]Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing,100088,China

出　　处：《Neuroscience Bulletin》2022年第10期1153-1169,共17页神经科学通报（英文版）

基　　金：This work was supported by the Beijing Natural Science Foundation(7192016 and 7222064);the Scientific Research Common Program of Beijing Municipal Commission of Education(KM201910025029);the National Natural Science Foundation of China(82071539 and 31972911).

摘　　要：Type 1 diabetes mellitus(T1DM)-induced cognitive dysfunction is common,but its underlying mechanisms are still poorly understood.In this study,we found that knockout of conventional protein kinase C(cPKC)γsignificantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles,but did not affect the activities of GSK-3βand PP2A in the hippocampal neurons of T1DM mice.cPKCγdeficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice.Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγdeficiency in T1DM mice.Moreover,cPKCγdeficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro.The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor.In conclusion,these results indicated that cPKCγpromotes autophagy through the AMPK/mTOR signaling pathway,thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.

关 键 词：Conventional protein kinase C(cPKC)γ Tau Phosphorylated Tau AUTOPHAGY AMPK/mTOR signaling pathway 

分 类 号：R749.16[医药卫生—神经病学与精神病学]