Effects of aerobic exercise on hippocampal SUMOylation in APP/PS1 transgenic mice

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease. SUMOylation, a post-translational modification, has been found to be dysregulated in the AD brain and to exacerbate learning and memory disabilities and increase amyloid beta (Aβ) expression further. To investigate whether exercise-induced alleviation of AD was associated with SUMOylation, which still remains unknown, 3-month-old C57BL/6 mice and APP/PS1 transgenic mice were randomly divided into the wild-type control (WC), wild-type exercise (WE), APP/PS1 control (AC), and APP/PS1 exercise (AE) groups. Mice in the exercise groups underwent a 3-month treadmill exercise regimen. We observed impaired learning and memory abilities in APP/PS1 mice, but the 3-month treadmill exercise regimen improved spatial learning and memory abilities in wild-type and APP/PS1 mice. In addition, senile plaques, SUMO1 mRNA, and SENP1 mRNA levels increased in the hippocampi of APP/PS1 mice. However, 3-month treadmill exercise decreased the levels of senile plaques, SUMO1 mRNA and SENP1 mRNA as well as may reduce SUMO1 modification in 6-month-old APP/PS1 mice, but SUMO2 mRNA expression, SUMO2/3 modification, and overall SUMOylation levels did not significantly change. Our results suggest that the impaired learning and memory abilities and aggregations of Aβ may relate to increased hippocampal SUMO1 transcription levels; the beneficial effects of treadmill exercise on learning and memory performances and AD pathogenesis may associated with the abatement of SUMO1 modification, but may not with SUMO2/3 modification.