The Effects And Underlying Mechanisms Of Quercetin Enrich Diet On Cognitive Improvement In An APP/PS1 Mouse Model Of Alzheimer’s Disease

Objective:The aim of this study was to evaluate the protective effects of dietary flavonoid quercetin against Alzheimer’s disease(AD)and detect the explicit AD ministration of quercetin in early-middle or middle-late stage of AD pathology could play the effect as well as its mechanism of action.In this study,APP/PS1 mice were used to investigate cognitive impairment and related pathologies in order to explore the prevention and treatment of Alzheimer’s disease,and provide experimental data for the prevention and treatment of quercetin in Alzheimer’s disease.Methods:1.The spatial learning ability of APP/PS1 mice with dietary flavonoid quercetin(1-13mo,1-9mo,6-13mo)was evaluated by Morris water maze test.2.The expression of GFAP in cerebral cortex and hippocampus of APP/PS1 mice fed a quercetin-rich diet(1-13mo)was detected by fluorescence immunoassay.The amyloid plaque and astrocyte proliferation in cerebral cortex and hippocampus were assessed.3.Detection of mRNA expression of Aβdeposition and astrocytes associated protein genes such as APP,BACE1,PS1,Smad2,STAT3,Hevin and SPACE in cerebral cortex and hippocampus of quercetin-rich diet group(1-9mo,6-13mo)through the real-time polymerase chain reaction.Also,detection ofβ-Secretase andγ-Secretase activity were measured by enzyme-linked immunosorbent assay(ELISA).4.Detection of associated protein expression on Aβdeposition and astrocytes of APP/PS1 mice with Quercetin enrich diet(1-13mo)such as APP,CTFβ,GFAP and associated protein including APP,CTFβ,BACE1,PS1,p-Smad2,Smad2,p-STAT3,STAT3,Hevin and SPACE of Quercetin enrich diet(1-9mo、6-13mo)by western-blot assay.Results:1.Relative to normal diet mice,the spatial learning ability and memory ability of APP/PS1 mice with Quercetin enrich diet(1-13mo)improved significantly,and the number of amyloid plaques and the area in cerebral cortex and hippocampus decreased obviously.The number of GFAP~+cells reduced,and the protein expression of APP,CTFβ,GFAP decreased in cerebral cortex and hippocampus.2.The Spatial learning ability and memory ability of APP/PS1 mice with quercetin enrich diet(1-9mo)improved relatived to normal diet mice.The activity ofβ-secretase reduced for APP/PS1 mice with quercetin enrich diet(1-9 mo),at the same time,the mRNA level of PS1,Hevin and SPACE reduced obviously.The protein level of CTFβ,PS1,p-Smad2,p-STAT3,Hevin and SPACE also decreased significantly.3.There is no significant difference between the APP/PS1 mice with quercetin enrich diet(6-13mo)and normal diet mice on the spatial learning ability and memory ability,the mRNA level of APP,BACE1 and PS1,the activity ofβ-secretase andγ-secretase,the mRNA level of Hevin,SPACE,Smad2,STAT3 to reflected astrocyte proliferation,and the protein level of APP,CTFβ,BACE1,PS1,p-Smad2,Smad2,p-STAT3,STAT3,Hevin and SPACE.Conclusion:Only quercetin enrich diet during the early-middle stage of AD pathological development period ameliorates cognitive dysfunction,and the protection effect was mainly related to increase Aβclearance and reduced astrogliosis.Quercetin enrich diet can improve astrocyte function,improve spatial learning and memory,prevent cognitive dysfunction,and improve cognitive dysfunction only in the early and middle stages of AD disease development by increasing clearance of Aβdeposition.Protection is associated with Aβclearance and reduction of astrocyte proliferation.