Abstract
Mechanisms underlying the protective effect of exercise training against the progression of Alzheimer's disease (AD) are not fully understood. This study investigated the effects of treadmill running on Aβ plaque burden and hyper-phosphorylated tau protein, neuro-inflammation, mitochondrial dysfunction, and adult neurogenesis markers in conjunction with cognitive impairments in triple transgenic AD (3xTg-AD) mice. At age of three months, the 3xTg-AD mice were assigned to control (AD, n = 10) or exercise training (AD-EXE, n = 10). The AD-EXE mice were trained on a rodent motor-driven treadmill with a frequency of 5 days per week for 12 weeks. As a consequence, AD-EXE mice had lower levels of Aβ plaque burden and neuro-inflammation, positive changes in mitochondrial function toward a more robust phenotype, and increases in hippocampal adult neurogenesis markers in the hippocampus and cerebral cortex compared to AD mice. The alleviating effects of treadmill running against the progression of the disease were accompanied by enhanced AD-like cognitive performances based on Morris water maze. The current findings support and extend previous studies reporting the protective effect of physical exercise against the progression of the disease in AD animal models.