Effect of resveratrol on miRNA-106b in Alzheimer's disease animal model

Abstract

Objective To investigate the effect of resveratrol on miRNA-106b in Alzheimer's disease (AD) animal model. Methods Fifty Kunming male mice were divided into five groups by completely randomized block sampling. The five groups included three dosage resveratrol groups, an AD model group and a control group. The AD models were established in one month prior to treatments. Subsequently, from the 31st day various doses of resveratrol were provided intragastricly for 60 days. Then the memory function was observed by the step-down test. Meanwhile, the varying expressions of APP, P62, ApoA1, miRNA-106b, ABCA1 were tested in each group to determine whether there is the binding site for miRNA-106b in APP 3'UTR sequence. Results Compared with the control group by step-down test, the memory function of the AD model group mice decreased in different degree, which in the drug treatment group was higher than that in the model group (P<0.05). Compared with the AD group, the expression of APP (1.131±0.035) in the drug treatment group was higher than that in the model group (0.652±0.026), while the P62 (0.412±0.022) and ApoA1 (0.534±0.032) were lower than the model group (all P<0.05). High and medium dose groups of resveratrol treatment reduced varying degrees of APP(0.733±0.018, 0.929±0.019, F=177.733) levels, and increased P62(0.954±0.035, 0.633±0.015, F=434.5) and ApoA1(1.042±0.051, 0.824±0.034, F=286.582)levels (all P<0.05). The expression of miRNA-106b (0.464±0.313) and ABCA1(0.293±0.042)in the model group was lower than that in the control group (miRNA-106b 1.064± 0.032, F=238.159; ABCA1 0.781±0.027, F=341.61; both P<0.05). The miRNA-106b (0.843 ±0.034, 0.601±0.012) and ABCA1 (0.882±0.025, 0.624±0.036) levels in the high, medium dose resveratrol treatment groups increased to different extent (both P<0.05). After the drug treatment, luciferase reporter vector experiments showed that the APP 3'UTR sequence contains the binding site of miRNA-106b. Conclusions APP is one of the target genes of miRNA-106b. Resveratrol is capable of improving AD by enhancing the expression of miRNA-106b and down-regulating the target genes including APP, P62 and ApoA1. This provides a new theoretical basis for the clinical treatment of AD. Key words: Resveratrol; Alzheimer disease; miRNA; Amyloid precursor protein