Efficacy and mechanism of metformin in a rat model of AD / 中风与神经疾病杂志

ABSTRACT

@#Objective　To observe the effects of metformin on learning and memory ability in Alzheimer’s disease (AD) rats,and to further explore the potential mechanism.Methods　Fifty male SD rats were randomly divided into normal group,sham group,model group and treatment group.AD model was established by injecting 5 μl Aβ25-35 (2 g/L) into the hippocampus,and the same amount of normal saline was injected into the sham group rats.The rats in the treatment group were given 100 mg/(kg·d) metformin by gavage for 2 weeks.The next day,the learning and memory ability of rats,the basic conditions of hippocampal cells,and the relative expression levels of PI3K,AKT,P-AKT,GSK3β,P-GSK3β,tau ［PS202］ and tau5 in hippocampal tissues of rats in each group were detected.Results　Metformin significantly improved the cognitive ability of AD model rats (P<0.05).No significant difference in the basic morphological structure of hippocampal cells among all groups was observed.Compared with the normal and sham group,the expression levels of PI3K,P-AKT/AKT,P-GSK3β/GSK3β in the hippocampus of the model rats were significantly down-regulated (P<0.05),which were improved after metformin intervention (P<0.05).The expression of tau［pS202］/tau5 in the model group was significantly higher than that in the normal group and the sham group,and the phosphorylation of tau protein decreased after treatment (P<0.05).Conclusion　Metformin can effectively improve the learning and memory ability of AD model rats.Interestingly,the mechanism may be closely related to the “PI3K-AKT-GSK3β-tau phosphorylation” signaling pathway.