Oleanolic acid could ameliorate Aβ-induced spatial learning and memory loss. - GreenMedInfo Summary
Oleanolic Acid Ameliorates Aβ25-35 Injection-induced Spatial Learning and Memory Deficit in Alzheimer's Disease Model Rats.
CNS Neurol Disord Drug Targets. 2018 May 24. Epub 2018 May 24. PMID: 29793416
BACKGROUND: Abnormal amyloidβ (Aβ) accumulation and deposition in hippocampus is an essential process in Alzheimer's disease (AD).
OBJECTIVE: To investigate whether Oleanolic acid (OA) could improve learning and memory deficit 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 investigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the key targets of synapse, electrophysiology for long-term potentiation (LTP), and Ca2+ concentration in synapse was also measured.
RESULTS: The latency time in model group was significantly longer than that in sham operation group (P=0.0001<0.05); while it was significantly shorter in the OA group than that in model group (P=0.0001<0.05); compared with model group, the times of cross-platform in OA group significantly increased (P = 0.0001<0.05). TEM results showed OA couldalleviate neuron damage and synapses changes induced by Aβ25-35. The expression of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were significantly improved by OA; the concentration of Ca2+ were significantly lower and the slope and amplitude of f-EPSP increased in OA group.
CONCLUSIONS: OA could ameliorate Aβ-induced spatial learning and memory loss of AD rats, and the mechanism might be involved with maintaining synaptic integrity to restore synaptic plasticity and increasing the NMDAR2B protein, CaMKII and PKC protein in postsynaptic density (PSD), reducing synaptic Ca2+ concentration, enhancing LTPby up-regulating BDNF, TrkB, CREB proteins.