Oleanolic Acid Ameliorates Aβ25-35 Injection-induced Memory Deficit in Alzheimer's Disease Model Rats by Maintaining Synaptic Plasticity

• Published in: CNS & neurological disorders drug targets Vol. 17; no. 5; p. 389
• Main Authors: Wang, Kai, Sun, Weiming, Zhang, Linlin, Guo, Wei, Xu, Jiachun, Liu, Shuang, Zhou, Zhen, Zhang, Yulian
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2018
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - complications; Amyloid beta-Peptides - toxicity; Animals; Antipsychotic Agents - therapeutic use; Avoidance Learning - drug effects; Calcium - metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Disease Models, Animal; Electric Stimulation; Hippocampus - pathology; Hippocampus - ultrastructure; Long-Term Potentiation - drug effects; Male; Maze Learning - drug effects; Memory Disorders - drug therapy; Memory Disorders - etiology; Microscopy, Electron, Transmission; Oleanolic Acid - therapeutic use; Peptide Fragments - toxicity; Protein Kinase C - metabolism; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Signal Transduction - drug effects; Synapses - drug effects; Synapses - ultrastructure; Synaptic Potentials - drug effects; Aβ; synaptic plasticity; Ca2; Alzheimer's disease; Oleanolic acid; long-term potentiation
• ISSN: 1996-3181
• DOI: 10.2174/1871527317666180525113109

Abnormal amyloid β (Aβ) accumulation and deposition in the hippocampus is an essential process in Alzheimer's disease (AD). To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism. 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 investigate 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+ concentration in synapse was also measured. 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 significantly 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. The present results support that OA could ameliorate Aβ-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus.