Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, China.
Neurosci Bull. 2020 Jul;36(7):719-732. doi: 10.1007/s12264-020-00478-7. Epub 2020 Mar 20.
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.
嘌呤能受体已被报道参与脑疾病。在这项研究中，我们探讨了它们在 2 型糖尿病（T2DM）大鼠记忆障碍中的作用和机制。与对照组相比，T2DM 大鼠在 T 迷宫和 Morris 水迷宫（MWM）中的表现更差。T2DM 大鼠海马 P2X 嘌呤受体 4（P2X4R）阳性小胶质细胞减少，激活的小胶质细胞增加。长扩增子 PCR（LA-PCR）显示，T2DM 大鼠海马中 p2x4r 基因的 DNA 扩增较低。米诺环素显著减少了 T2DM 大鼠在 MWM 中激活的小胶质细胞数量和平均行进距离。最重要的是，P2X4R 的过表达抑制了小胶质细胞的激活，并挽救了 T2DM 大鼠的记忆障碍。总的来说，T2DM 导致海马中过度激活的小胶质细胞，部分原因是 DNA 损伤介导的 P2X4Rs 下调，从而导致记忆障碍。
