DietaryAdvancedGlycationEnd Products–InducedCognitive Impairment in Aged ICR Mice: Protective Role of Quercetin

Scope Dietary advanced glycation products (dAGEs) have been reported to induce cognitive impairment while quercetin possesses potential neuroprotective effects. The aim is to explore whether dAGEs would induce similar cognitive impairment from both young and aged ICR mice, and the protective effects of quercetin. Methods and results A total of 32 aged ICR mice (15‐month‐old) and 16 young ICR mice (3‐month‐old) are randomly assigned into the following six groups: Young mice control group, young mice fed with AGEs diet group, old mice control group, old mice fed with AGEs diet group, old mice with quercetin supplemented diet group, old mice fed with AGE diet supplemented with quercetin group. Dietary AGEs induced cognitive impairment only in aged, but not in young, ICR mice, while quercetin intervention is capable of reversing dAGEs‐induced cognitive dysfunction. This may be since quercetin 1) increased miR‐219, miR‐15a, and miR‐132 expression, inhibited p‐ERK1/2, and tau phosphorylation; and 2) improved gut microbiota richness and diversity, inhibited phylum Tenericutes and Proteobacteria, and elevated butyric acid from cecum. Conclusion Prolonged application of quercetin may be beneficial in the elderly, especially for those with high consumption of dAGEs. Dietary advanced glycation end products (AGEs) induces cognitive impairment only in aged ICR mice, while quercetin intervention reverses dAGEs‐induced cognitive dysfunction. This might be due to increased miR‐219, miR‐15a, and miR‐132 expression along with inhibited p‐ERK1/2 and tau phosphorylation; or improved gut microbiota richness and diversity, inhibited phylum Tenericutes and Proteobacteria, and elevated butyric acid from cecum.