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 ۱ (Fn۱). 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, ۳۰ aged C۵۷BL/۶ mice (weight: ۳۰ g) with AD were randomly assigned to one of the five groups: (۱) Control, (۲) AD, (۳) AD + Fisetin, (۴) AD + HIIT, and (۵) AD + HIIT + Fisetin. Alzheimer's disease was induced in the AD groups by injecting amyloid-beta (Aβ۱-۴۲) into the hippocampus. The HIIT protocol consisted of a ۱۰-minute warm-up at ۵۰-۵۵% VO۲ max, followed by seven intervals, each comprising ۴ minutes at ۸۰-۹۰% VO۲ max and ۳ minutes at ۶۵-۷۵% VO۲ max. Fisetin was administered at ۲۰ mg/kg for eight weeks. Data were analyzed using one-way ANOVA with a significance level of P ≤ ۰.۰۵. Results: Significant differences were observed in BDNF, Fn۱, and Aβ gene expression levels across the five groups of aged mice (p < ۰.۰۰۱). BDNF and Fn۱ expression were significantly reduced in the AD groups compared to the healthy controls (p < ۰.۰۰۱). However, their expression levels increased significantly in the AD + Training + Fisetin, AD + Training, and AD + Fisetin groups compared to the AD-only group (p < ۰.۰۰۱). The AD + Training + Fisetin group exhibited the highest expression levels, followed by the AD + Training and AD + Fisetin groups (p < ۰.۰۰۱). Aβ expression was significantly reduced in all intervention groups, with the AD + Training + Fisetin group showing the most substantial decrease (p < ۰.۰۰۱). Conclusion: Combining HIIT and fisetin supplementation may promote cerebral neurogenesis in AD by reducing Aβ levels and enhancing BDNF and Fn۱ 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.

کلیدواژه ها:

High-intensity interval training ، BDNF ، Fn۱ ، Fisetin ، Alzheimer's disease