DNA hypomethylation promotes learning and memory recovery in a rat model of cerebral ischemia/reperfusion injury  

作　　者：Guang Shi Juan Feng Ling-Yan Jian Xin-Yu Fan 

机构地区：[1]Department of Neurology,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China [2]Department of Neurology,The People’s Hospital of Liaoning Province,Shenyang,Liaoning Province,China [3]Department of Pharmacy,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China

出　　处：《Neural Regeneration Research》2023年第4期863-868,共6页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.82101567;Doctoral Start-up Foundation of Liaoning Province,No.2021-BS-111;345 Talent Project of Shengjing Hospital of China Medical University,No.M0673(all to XYF)。

摘　　要：Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.

关 键 词：cognitive memory DNA methylation DNMT1 hippocampus ISCHEMIA/REPERFUSION social memory spatial memory TET1 transient middle cerebral artery occlusion 5-aza-2′-deoxycytidine 

分 类 号：R743.34[医药卫生—神经病学与精神病学]