the effect of fisetin supplementation and high-intensity interval training on neurogenesis markers in aged alzheimer’s model mice

Introduction: alzheimer’s disease (ad) is associated with a marked reduction in brain-derived neurotrophic factor (bdnf) and fibronectin 1 (fn1). this study investigates the effects of fisetin supplementation combined with high-intensity interval training (hiit) on these neurogenesis markers in an aged mouse model of ad. methods: in this experimental study, 30 aged c57bl/6 mice (weight: 30 g) with ad were randomly assigned to one of the five groups: (1) control, (2) ad, (3) ad + fisetin, (4) ad + hiit, and (5) ad + hiit + fisetin. alzheimer’s disease was induced in the ad groups by injecting amyloid-beta (aβ1-42) into the hippocampus. the hiit protocol consisted of a 10-minute warm-up at 50-55% vo2 max, followed by seven intervals, each comprising 4 minutes at 80-90% vo2 max and 3 minutes at 65-75% vo2 max. fisetin was administered at 20 mg/kg for eight weeks. data were analyzed using one-way anova with a significance level of p ≤ 0.05. results: significant differences were observed in bdnf, fn1, and aβ gene expression levels across the five groups of aged mice (p < 0.001). bdnf and fn1 expression were significantly reduced in the ad groups compared to the healthy controls (p < 0.001). however, their expression levels increased significantly in the ad + training + fisetin, ad + training, and ad + fisetin groups compared to the ad-only group (p < 0.001). the ad + training + fisetin group exhibited the highest expression levels, followed by the ad + training and ad + fisetin groups (p < 0.001). aβ expression was significantly reduced in all intervention groups, with the ad + training + fisetin group showing the most substantial decrease (p < 0.001). conclusion: combining hiit and fisetin supplementation may promote cerebral neurogenesis in ad by reducing aβ levels and enhancing bdnf and fn1 gene expression. notably, the combined intervention of hiit and fisetin exhibits a more significant effect than either hiit or fisetin alone, with hiit being more effective than fisetin as a standalone treatment. thus, the combination of hiit and fisetin appears to be the most effective complementary approach for managing this disease.