Effects of Pretreatment With Coenzyme Q10 (CoQ10) and High-Intensity Interval Training (HIIT) on FNDC5, Irisin, and BDNF Levels, and Amyloid-Beta (Aβ) Plaque Formation in the Hippocampus of Aβ-Induced Alzheimer's Disease Rats

Aims Physical exercise has been shown to protect against cognitive decline in Alzheimer's disease (AD), likely through the upregulation of brain-derived neurotrophic factor (BDNF). Recent studies have reported that exercise activates the FNDC5/irisin pathway in the hippocampus of mice, triggering a neuroprotective gene program that includes BDNF. This study aimed to investigate the effects of 8 weeks of pretreatment with coenzyme Q10 (CoQ10) and high-intensity interval training (HIIT), both individually and in combination, on FNDC5, irisin, BDNF, and amyloid-beta (A beta) plaque formation in the hippocampus of A beta-related AD rats. Methods In this study, 72 male Wistar rats were randomly assigned to one of the following groups: control, sham, HIIT (low intensity: 3 min running at 50%-60% VO2max; high intensity: 4 min running at 85%-90% VO2max), Q10 (50 mg/kg, orally administered), Q10 + HIIT, AD, AD + HIIT, AD + Q10, and AD + Q10 + HIIT. Results A beta injection resulted in a trend toward decreased levels of FNDC5, irisin, and BDNF, alongside increased A beta plaque formation in the hippocampus of A beta-induced AD rats. However, pretreatment with CoQ10, HIIT, or their combination significantly restored hippocampal levels of FNDC5, irisin, and BDNF, while also inhibiting A beta plaque accumulation in these rats. Conclusion Pretreatment with CoQ10 and HIIT improved the A beta-induced reduction in BDNF levels probably through the FNDC5/irisin pathway and preventing A beta plaque formation.