Aerobic Exercise Combined with Antioxidative Treatment does not Counteract Moderate- or Mid-Stage Alzheimer-Like Pathophysiology of APP/PS1 Mice

AimsThe present study evaluated the combined treatment effects of aerobic exercise and antioxidative stress on moderate-stage Alzheimer's disease (AD). MethodsTen-month-old APP/PS1 mice were given antioxidative treatment with acetylcysteine, along with aerobic exercise for 6weeks. Spatial learning and memory were tested using the Morris water maze, and -amyloid (A) plaque deposits in the forebrain were quantified by Thioflavin-S staining. Levels of soluble A1-42, -secretase enzyme, ?-secretase enzyme, oxidative and antioxidant stress markers nitrotyrosine and peroxiredoxin-1, glial markers glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1, and synaptic protein synaptophysin in the hippocampus were all measured by western blotting and/or immunohistochemistry. ResultsAPP/PS1 mice showed severe declines in spatial learning and memory compared with their wild-type littermates, which were not attenuated by aerobic exercise combined with antioxidative treatment. The pathologic analysis revealed that A deposition and production, oxidative stress, glial inflammation, and synaptic loss were not mitigated in the brain of exercised APP/PS1 mice, compared with the sedentary APP/PS1 animals. ConclusionThis study reveals that a combined treatment of aerobic exercise plus antioxidative stress does not counteract pathophysiology in the moderate- or mid-stages of AD.