Effects of Treadmill Running on Oxidative Stress and Heat Shock Protein in Early Stage of 3xTg-AD Mice

Abstract

PURPOSE The mechanisms underlying the protective effects of exercise training against cognitive decline are not fully understood. This study aimed to investigate the effects of treadmill running on oxidative stress and heat shock protein levels in a mouse model of early stage triple transgenic Alzheimer’s disease (3xTg-AD). METHODS We divided 5-month old 3xTg-AD mice (N=20) into the control (AD+CON, n=10) and exercise training (AD+EX, n=10) groups. Background strain mice were included as wild-type controls (WT, n=10). AD+EX mice were subjected to treadmill running at a speed of 15 m/min, 50 min/day, 5 days/week for 12 weeks. RESULTS Treadmill running protected 3xTg-AD mice from cognitive decline and significantly suppressed the increase in soluble Aβ1-42 protein levels (AD+CON vs AD+EX, p=0.015) and the progression of oxidative damage. This was evidenced by significant increase in anti-oxidative protein levels such as superoxide dismutase-1 (SOD-1), heme oxygenase (HO-1) and heat shock protein 70 (HSP70) in the hippocampus of AD+EX mice compared to AD+CON mice. Moreover, the brain-derived neurotrophic factor (BDNF) and synaptic proteins such as PSD95 and synaptophysin were upregulated in AD+EX mice compared to AD+CON mice. CONCLUSIONS Our findings support and extend previous studies reporting the preventive effects of exercise training on the pathological processes of the Alzheimer’s disease in the 3xTg AD mouse model.

Keywords

• alzheimer’s disease
• treadmill running
• oxidative stress
• heat shock protein
• 3xtg-ad