Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes  

作　　者：Ping-An Zhang Qian Sun Yong-Chang Li Rui-Xia Weng Rui Wu Hong-Hong Zhang Guang-Yin Xu 

机构地区：[1]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience,Soochow University,Suzhou 215123,China [2]Center for Translational Medicine,The Affiliated Zhangjiagang Hospital of Soochow University,Suzhou 215600,China [3]The Second Affiliated Hospital of Soochow University,Suzhou 215004,China

出　　处：《Neuroscience Bulletin》2020年第7期719-732,共14页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (31730040,81801115, and 81920108016);the China Postdoctoral Science Foundation (2018M642304);the Priority Academic Program Development of Jiangsu Higher Education Institutions of China。

摘　　要：Purinergic receptors have been reported to be involved in brain disorders.In this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats exhibited a worse performance in the T-maze and Morris water maze(MWM) than controls.Microglia positive for P2 X purinoceptor 4(P2 X4 R) in the hippocampus were reduced and activated microglia were increased in T2 DM rats.Long Amplicon PCR(LA-PCR) showed that DNA amplification of the p2 x4 r gene in the hippocampus was lower in T2 DM rats.Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2 DM rats in the MWM.Most importantly,P2 X4 R overexpression suppressed the activated microglia and rescued the memory impairment of T2 DM rats.Overall,T2 DM led to excessive activation of microglia in the hippocampus,partly through the DNA damagemediated downregulation of P2 X4 Rs,thus contributing to memory impairment.

关 键 词：MICROGLIA P2X4 receptors DNA damage Type 2 diabetes mellitus Memory impairment 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学]