Effects of exercise intensity on spatial memory performance and hippocampal synaptic function in SAMP8 mice

Learning and memory impairment is commonly noted in Alzheimer's disease (AD), which is regarded as a progressive synaptic failure disease. Exercise is a nonpharmacological strategy that may help prevent cognitive decline and reduce the risk of AD, which is usually thought to be related to synaptic damage in the hippocampus. However, the effects of exercise intensity on hippocampal memory and synaptic function in AD remain unclear. In this study, senescence-accelerated mouse prone-8 (SAMP8) mice were randomly assigned to the control group (Con), low-intensity exercise group (Low), and moderate-intensity exercise group (Mid). Here, we showed that eight weeks of treadmill exercise beginning in four-month-old mice improved spatial memory and recognition memory in six-month-old SAMP8 mice, while the Con group exhibited impaired spatial memory and recognition memory. Treadmill exercise also improved hippocampal neuron morphology in SAMP8 mice. Furthermore, dendritic spine density and the levels of postsynaptic density protein-95 (PSD95) and Synaptophysin (SYN) increased significantly in the Low and Mid groups as compared with the Con group. We further showed that moderate-intensity exercise (60 % of maximum speed) was more efficacious in increasing dendritic spine density、PSD95 and SYN, than low-intensity exercise (40 % of maximum speed). In conclusion, the positive effect of treadmill exercise is closely related to exercise intensity, with moderate-intensity exercise showing the most optimal effects.