PMID- 32198702 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20210719 IS - 1995-8218 (Electronic) IS - 1673-7067 (Print) IS - 1995-8218 (Linking) VI - 36 IP - 7 DP - 2020 Jul TI - Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes. PG - 719-732 LID - 10.1007/s12264-020-00478-7 [doi] AB - 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 (T2DM). T2DM rats exhibited a worse performance in the T-maze and Morris water maze (MWM) than controls. Microglia positive for P2X purinoceptor 4 (P2X4R) in the hippocampus were reduced and activated microglia were increased in T2DM rats. Long Amplicon PCR (LA-PCR) showed that DNA amplification of the p2x4r gene in the hippocampus was lower in T2DM rats. Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2DM rats in the MWM. Most importantly, P2X4R overexpression suppressed the activated microglia and rescued the memory impairment of T2DM rats. Overall, T2DM led to excessive activation of microglia in the hippocampus, partly through the DNA damage-mediated downregulation of P2X4Rs, thus contributing to memory impairment. FAU - Zhang, Ping-An AU - Zhang PA AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China. AD - Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, China. FAU - Sun, Qian AU - Sun Q AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China. FAU - Li, Yong-Chang AU - Li YC AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China. FAU - Weng, Rui-Xia AU - Weng RX AD - The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. FAU - Wu, Rui AU - Wu R AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China. FAU - Zhang, Hong-Hong AU - Zhang HH AD - The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. FAU - Xu, Guang-Yin AU - Xu GY AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China. guangyinxu@suda.edu.cn. AD - Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, China. guangyinxu@suda.edu.cn. LA - eng PT - Journal Article DEP - 20200320 PL - Singapore TA - Neurosci Bull JT - Neuroscience bulletin JID - 101256850 RN - 0 (Receptors, Purinergic P2X4) SB - IM MH - Animals MH - Cognition Disorders/etiology/*genetics MH - *Diabetes Mellitus, Type 2/complications MH - Hippocampus MH - Male MH - Microglia MH - Rats MH - Rats, Sprague-Dawley MH - *Receptors, Purinergic P2X4/genetics PMC - PMC7340685 OTO - NOTNLM OT - DNA damage OT - Memory impairment OT - Microglia OT - P2X4 receptors OT - Type 2 diabetes mellitus COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2020/03/22 06:00 MHDA- 2021/07/20 06:00 PMCR- 2020/03/20 CRDT- 2020/03/22 06:00 PHST- 2019/08/23 00:00 [received] PHST- 2019/11/25 00:00 [accepted] PHST- 2020/03/22 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] PHST- 2020/03/22 06:00 [entrez] PHST- 2020/03/20 00:00 [pmc-release] AID - 10.1007/s12264-020-00478-7 [pii] AID - 478 [pii] AID - 10.1007/s12264-020-00478-7 [doi] PST - ppublish SO - Neurosci Bull. 2020 Jul;36(7):719-732. doi: 10.1007/s12264-020-00478-7. Epub 2020 Mar 20.