Abstract: BACKGROUND: Beta-amyloid (Aβ) accumulation and deposition in the hippocampus can affect synaptic morphology and function, resulting in impaired synaptic plasticity, which is considered to be the root cause of learning and memory deficits of Alzheimer’s disease. It is not yet clear whether aerobic exercise can alleviate Aβ-induced synaptic damage and improve the learning and memory abilities of patients with Alzheimer’s disease. 
OBJECTIVE: To observe the effect of aerobic exercise on the hippocampal synaptic structure and synapse marker proteins, synaptophysin and postsynaptic dense 95, in a rat model of Alzheimer’s disease induced by Aβ1-42, so as to investigate the mechanism by which aerobic exercise influences learning and memory ability of patients with Alzheimer’s disease. 
METHODS: Eighty healthy Sprague-Dawley rats were randomly divided into four groups (n=20 per group): control group, exercise group, Aβ1-42 model group, and Aβ1-42 exercise group. Rats in the latter two groups were injected with 10 μL of Aβ1-42 (1 μg/μL) into the bilateral hippocampi, while those animals in the former two groups were injected 10 μL of normal saline in the same way. Rats in the two exercise groups began aerobic exercise training on the 2nd day after injection and the training lasted for 5 weeks, 6 days per week. Morris water maze test was conducted to test the spatial learning and memory ability of rats. Then brain tissue samples of rats were taken. The hippocampal synaptic structure and the expression of synaptophysin and postsynaptic dense 95 in the hippocampus were detected by electron microscopy, immunofluorescence, and western blot assay. 
RESULTS AND CONCLUSION: (1) In the Morris water maze test, the average escape latency of all rats was gradually shortened during the location-based navigation training. The average escape latency decline rate of the Aβ1-42 exercise group was slower than that of the control group but showed a faster trend compared with that of the Aβ1-42 model group. (2) In the space exploration experiment, the frequency of platform crossing and retention time in the target quadrant were significantly lower in the Aβ1-42 exercise and Aβ1-42 model groups than the control group (P < 0.01, P < 0.05), but were significantly increased in the Aβ1-42 exercise than the Aβ1-42 control group (P < 0.05). Moreover, there was no significant difference between the exercise and control groups (P > 0.05). (3) Under the electron microscope, compared with the control group, the number of synapses decreased (P < 0.01) and the thickness of postsynaptic compacts became thinner in the Aβ1-42 model group (P < 0.05). Compared with the Aβ1-42 model group, the Aβ1-42 exercise group had an increase in the number of synapses (P < 0.05) and the thickness of postsynaptic compacts (P < 0.05). (4) Results from the immunofluorescence and western blot detections showed that the expressions of postsynaptic dense 95 and synaptophysin in the hippocampus were significantly lower in the Aβ1-42 model group than the control group (P < 0.01, P < 0.05), while the expression levels in the Aβ1-42 exercise group was significantly higher than those in the Aβ1-42 model group (P < 0.01, P < 0.05). (5) These findings indicate that aerobic exercise can effectively reduce Aβ1-42-induced damage to the hippocampal synaptic structure and promote the expression of hippocampal postsynaptic dense 95 and synaptophysin in rats, which may be one of the mechanisms by which aerobic exercise alleviates the learning and memory impairment in Alzheimer’s disease rats caused by Aβ1-42 toxicity.

Key words: Alzheimer’s disease, aerobic exercise, hippocampus, synaptic structure, synaptic protein