Dietary advanced glycation end products induced anxiety- and depression-like behaviors in female C57BL/6 mice and the ameliorative effects of quercetin.

Quercetin is a flavonoid bioactive compound with potential anti-depression effect. Dietary advanced glycation end-products (AGEs) might be critically associated with depression. We aimed to explore whether quercetin ameliorates dietary AGEs-induced anxiety and depression-like behaviors in female mice, with a focus on hypothalamic-pituitary-adrenal (HPA) axis regulation and gut microbiota composition. Mice were divided into three groups: control, dietary AGEs, and AGEs plus quercetin. Dietary AGEs induced anxiety and depression-like behavioral effects, reduced brain-derived neurotrophic factor, P-CREB (phosphorylated cyclic adenosine monophosphate response element-binding protein), post-synaptic density protein-95, doublecortin, and synaptophysin protein expression. Dietary AGEs induced HPA axis overactivation has been confirmed by decreased hippocampal glucocorticoid receptor, phospho-glucocorticoid receptor Ser211, and arginase-1, and elevated FK506 binding protein 51, NOD-like receptor thermal protein domain associated protein 3, caspase-1, and p65 protein expression. Dietary AGEs resulted in gut microbiota disorder and correlation analysis revealed significant associations between Proteobacteria, the [Eubacterium] coprostanoligenes group, Klebsiella and Lachnospiraceae_NK4A136_group with behavioral parameters. Quercetin intervention improved dietary AGEs associated anxiety and depression-like behavioral effects via restoring HPA axis and gut microbiota.