Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes.
10.1007/s12264-020-00478-7
- Author:
Ping-An ZHANG
1
;
Qian SUN
1
;
Yong-Chang LI
1
;
Rui-Xia WENG
2
;
Rui WU
1
;
Hong-Hong ZHANG
2
;
Guang-Yin XU
3
Author Information
1. Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
2. The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
3. Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China. guangyinxu@suda.edu.cn.
- Publication Type:Journal Article
- Keywords:
DNA damage;
Memory impairment;
Microglia;
P2X4 receptors;
Type 2 diabetes mellitus
- From:
Neuroscience Bulletin
2020;36(7):719-732
- CountryChina
- Language:English
-
Abstract:
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.
