Oleanolic Acid Ameliorates Aβ(25-35) Injection-induced Memory Deficit in Alzheimer’s Disease Model Rats by Maintaining Synaptic Plasticity

BACKGROUND: Abnormal amyloid β (Aβ) accumulation and deposition in the hippocampus is an essential process in Alzheimer’s disease (AD). OBJECTIVE: To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism. METHODS: Forty-five SD rats were randomly divided into sham operation group, model group, and OA group. AD models by injection of Aβ25-35 were built. Morris water maze (MWM) was applied to inves-tigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the proteins, electrophysiology for long-term potentiation (LTP), and Ca2+ con-centration in synapse was also measured. RESULTS: The latency time in model group was significantly longer than that in sham operation group (P=0.0001); while it was significantly shorter in the OA group than that in model group (P=0.0001); compared with model group, the times of cross-platform in OA group significantly increased (P=0.0001). TEM results showed OA could alleviate neuron damage and synapses changes induced by Aβ25-35. The expressions of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were signif-icantly improved by OA (P=0.0001, 0.036, 0.041, 0.0001, 0.0001, 0.026, respectively) compared with that in model group; the concentration of Ca2+ was significantly lower in OA group (1.11±0.42) than that in model group (1.68±0.18); and the slope rate (P=0.0001) and amplitude (P=0.0001) of f-EPSP significantly increased in OA group. CONCLUSION: The present results support that OA could ameliorate Aβ-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus