Treadmill exercise overcomes memory deficits related to synaptic plasticity through modulating ionic glutamate receptors

Abstract

Neuronal death and synaptic loss are major pathogensis of Alzheimer’s disease (AD), which may be related to the ionic glutamate receptors abnormality. Ionic glutamate receptors are important postsynaptic membrane receptors that regulate excitatory synaptic transmission and are also major component of the postsynaptic density. Beta-Amyloid (Aβ) attacks ionic glutamate receptors to reduce synaptic efficacy and synaptic plasticity, resulting in neuronal death and synaptic loss. The current study aimed to investigate whether exercise-ameliorated AD was associated with changes in ionic glutamate receptors. Transgenic APP/PS1 mice (TgAPP/PS1) and age-matched littermate wild mice were divided into wild type control group, wild type exercise group, transgenic control group and transgenic exercise group. The mice in exercise groups were subjected to treadmill training for 12 weeks. The results showed that 12-week treadmill exercise improved the spatial learning and memory abilities of TgAPP/PS1 mice. Moreover, exercise decreased the contents of Aβ40, Aβ42 and amyloid plaque deposition in hippocampus of TgAPP/PS1 mice. The number of synapses and the length and thickness of postsynaptic densities (PSD) in the hippocampal CA1 region of TgAPP/PS1 mice were significantly increased after exercise. Concomitantly, TgAPP/PS1 displayed obstacles in synaptic plasticity as evidenced by significant decreases in the levels of synaptic structural plasticity-related proteins SYN, PSD95, MAP2 and NCAM, as well as ionic glutamate neuroreceptor subunit proteins GluN2B and GluA1. Interestingly, exercise alleviated these synaptic plasticity disorder in TgAPP/PS1 mice. Thus, this study demonstrates that 12-week treadmill exercise reduces Aβ levels in the hippocampus and mitigates cognitive decline in TgAPP/PS1 mice, which may be mediated by improvements in synaptic structural plasticity and excitatory neurotransmission.