Effects Of Salidroside On Cognitive Dysfunction By Regulating DNA Methylation In Diabetic Hippocampus

ObjectiveDNA methylation is closely related to the cognitive function.The aim of this study is to explore the effects of salidroside on diabetic cognitive dysfunction,and to investigate the potential underlying mechanisms of DNA methylation.MethodsThirty SD male rats were divided into three groups: normal group,diabetic group and salidroside treatment group,with 10 rats in each group.Except for the normal group,the other two groups were intraperitoneally given streptozotocin with 65 mg/kg to prepare the diabetic rat.Subsequently,the treatment group was given salidroside with 200 mg/kg per day by gavage.After 12 weeks,the Morris water maze was utilized to detect the learning and memory ability of rats,the DNA total methylation quantification kit detected the changes of total DNA methylation in the hippocampus of rats,Western blot detected the expression of DNA methyltransferase 1 and DNA methyltranserasse 3a in the hippocampus,immunohistochemistry detected the changes of 5-methylcytosine and microtuble associated protein-2 in the hippocampus,and Nissl staining detected the changes in the number of neurons in the hippocampus.ResultsThe results of the escape latency in the water maze directional navigation experiment in rats showed: comparing with the normal group,the escape latency of the diabetic group was significantly longer(P<0.001);comparing with the diabetic group,the escape of the salidroside group was significantly shortened(P<0.05).The results of the space exploration experiment showed: comparing with the normal group,the number of crossing platforms in the diabetic group was significantly reduced(P<0.01);comparing with the diabetes group,the number of crossing platforms in the salidroside group significantly increased(P<0.05).The results of total DNA methylation showed: comparing with the normal group,the total DNA methylation in the hippocampus of the diabetic group was significantly decreased(P<0.001);comparing with the diabetic group,the hippocampus of the salidroside group was significantly increased(P<0.01).Western blot results showed: comparing with the normal group,the expression of DNMTI and DNMT3 a in the hippocampus of the diabetic group was significantly decreased(P<0.001);comparing with the diabetic group,the expression of DNMT1 and DNMT3 a in the hippocampus of the salidroside group significantly increased(P<0.01).Immunohistochemical test results showed: comparing with the normal group,the expression of 5-mC and MAP-2 protein in the diabetic group decreased significantly(P<0.05);comparing with the diabetic group,the expression 5-mC,MAP-2 protein in the salidroside group was significantly increased(P<0.05).The results of Nissl staining showed: comparing with the normal group,the number of neurons in the hippocampus of the diabetic group significantly reduced(P<0.01);comparing with the diabetic group,the number of neurons in the salidroside group significantly increased(P< 0.05).conclusionsSalidroside treatment can significantly increase the total DNA methylation level and the expression level of DNMTI,DNMT3 a,5-mC,and MAP-2 in the hippocampus of the diabetic rat,and reduce the death of neurons in the hippocampus of the diabetic rat,thus can improve the learning and memory ability of rats.