Quercetin Attenuates Neurodegeneration In SAMP8 Mouse Via Modulation Of SIRT1

ObjectiveThe present study was designed to examine the effects of quercetin(QUER)on expression of AMP-activated protein kinase(AMPK),Sirtuin 1(SIRT1),peroxisome proliferator-activated receptor y(PPAR-y),brain-derived neurotropic factor(BDNF)levels and endoplasmic reticulum stress(ER Stress)in the hippocampus of SAMP8 mice to determine how quercetin attenuates neurodegeneration in late-onset/age-related AD brain.MethodsMice were randomly divided into four groups(n=10)as follows:the SAMR1 control group(CON group,0.1%DMSO,water,orally),the SAMP8 model group(MOD group,0.1%DMSO,water,orally),low dose QUER group(QUER L group,25mg/kg,orally),high dose QUER group(QUER H group,50 mg/kg,orally),Salubrinal group(SAL group,25mg/kg,ip.).Mice were orally administered of QUER or intraperitoneally injected of SAL,once per day for 28 days.The Morris water maze was used to test spatial learning and memory performance.Nissl staining and Hematoxylin-eosin staining were performed to analyze the hippocampal histopathological damage.Western blotting and detection kit were used to detect BIP,eIF2?,p-eIF2?,CHOP,SIRT1,AMPK,p-AMPK,PPAR-?,BDNF expression and levels of MDA and ROS in the hippocampus.Experimental values were expressed as means ± SEM or means ± SD.Differences between groups were evaluated on Student's unpaired t-test using the SPSS 19.0 software.Differences among multi groups were performed using Two-way analysisof variance(ANOVA).A P<0.05 considered as statistically significant.ResultsThere are significant dysfunction of learning and memory,hippocampal histopathological abnormalities and decreased BDNF levels in the hippocampus.QUER treatment significantly improved learning and memory function,attenuated hippocampal histopathological abnormalities,up-regulates SIRT1,PPAR-? and BDNF expression,attenuated ER stress,relieved oxidative stress and activates AMPK phosphorylation in the hippocampus.ConclusionConclusively,our data suggest quercetin could alleviate central nervous system neurodegeneration by upregulating AMPK,SIRT1,PPAR-? and BDNF expression in SAMP8 mice brain.QUER also relieves oxidative stress in SAMP8 mice brain.