The Effect of Treadmill Running on Insulin Receptor, Oxidative Stress, and Impaired Synaptic Plasticity in the Brain of High Fat Diet-induced 3xTg-AD Mice

Abstract

PURPOSE This study investigated the effect of treadmill running on obesity-related brain insulin receptor, oxidative stress, and impaired synaptic plasticity in 3xTg-AD mice (APPSWE, PS1M146V and tauP301L). METHODS At 4 months of age, thirty 3xTg-AD mice were assigned to standard chow (SC, n=10) or high-fat-diet (HFD, n=10) or HFD plus exercise training (HFD+EX, n=10). HFD+EX mice were subjected to treadmill running at a moderate intensity with duration of 30 minutes per day and frequency of 5 days per week for 20 weeks. HFD mice were fed a 60% fat HFD for the same period. Mice were sacrificed and histological and western blot analysis was performed. RESULTS Compared with the SC mice, the HFD mice had significantly lower levels of p-IRβ/IRβ (p<.05) in conjunction with APP (p<.05), Aβ oligomer (p<.05), HNE/NEUN (p<.05), PSD95 (p<.05), DCX/NeuN (p<.05) in the hippocampus. On the other hand, we found that treadmill running attenuated HFD-induced exacerbations of APP (p<.05), Aβ oligomer (p<.05), PSD95 (p<.05), DCX/NeuN (p<.05) in the hippocampus. CONCLUSIONS The current findings suggest that treadmill running protects against AD-like disease progression and impaired synaptic plasticity, cell proliferation caused by a HFD in the 3xTg-AD mice.

Keywords

• exercise training
• alzheimer disease
• high fat diet
• 3xtg-ad mice