Effect of Daphnetin on Autophagy in Alzheimer's Disease Model Mice

OBJECTIVE To explore the effect of daphnetin on autophagy in Alzheimer's disease(AD) and its mechanism of neuroprotection in AD. METHODS Drugs were administered to 3-month old APP/PS1 double transgenic mice. After 3 months of drug treatment, the effect of daphnetin on spatial exploration and memory in AD model mice was observed by Morris water maze test; ELISA kits were used to detect the levels of Aβ_1-40 and Aβ_1-42 in the hippocampus of AD model mice. Western blotting was used to detect the effect of daphnetin on microtubule-associated protein light chain 3 Ⅱ(LC3-Ⅱ), beclin-1 and the effect of p62 expression level. RESULTS Morris water maze test showed that the escape latency of APP/PS1 double transgenic mice was significantly longer than that of the control group, and the residence time of the original quadrant was significantly shorter. The escape latency of daphnetin group was significantly shorter and the residence time of the original quadrant was prolonged compared with the model group. Compared with the control group, the levels of Aβ in the brain of APP/PS1 double transgenic mice were increased, and the levels of Aβ in daphnetin group were significantly decreased. Western blotting results showed that LC3-Ⅱ and beclin-1 in hippocampus of AD model mice decreased significantly, daphnetin increased the expression of LC3-Ⅱ and beclin-1 and inhibited the protein expression of p62. CONCLUSION Daphnetin enhances autophagy by up regulating LC3-Ⅱ and beclin-1 proteins and improves the learning and memory function of AD mice.