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

ABSTRACT: 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.

SUBMITTER: Shi G 

PROVIDER: S-EPMC9700107 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature