Treadmill exercise prevents decline in spatial learning and memory in APP/PS1 transgenic mice through improvement of hippocampal long-term potentiation

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease clinically characterized by learning and memory function deterioration. While it is well established that exercise can improve cognitive performance in AD, there have been few basic cellular and molecular mechanisms research performed to test the interaction between exercise and AD. In this study, we aimed at investigating whether treadmill exercise improves learning and memory function in APP/PS1 transgenic mouse model of Alzheimer's disease by enhancing long-term potentiation (LTP) and up-regulation of brain-derived neurotrophic factor (BDNF) mRNA expression. Our results show that, in comparison to wild type mice, transgenic mice were characterized by impaired learning and memory function, LTP deficits and increased BDNF mRNA levels. Treadmill exercise enhanced learning and memory function not only in wild type mice but also in APP/PS1 mice paralleled by LTP. However, BDNF has emerged as a crucial regulator of synaptic plasticity mechanisms underlying learning and memory in wild-type mice, but not in APP/PS1 mice. Hence, this investigation demonstrates that treadmill exercise is an effective therapeutic that alleviate learning and memory decline in APP/PS1 mouse model, and enhanced LTP maybe a cellular mechanism involved in neuropathological course of AD and cognitive improvement induced by exercise.