Effects of oleanolic acid on learning and memory, synaptic morphology and the expression of CREB in the hippocampus and cereberal cortex of SAMP8 mice

Abstract

Objective To observe the influence of oleanolic acid on the ethology of 9-month-old mice, the completeness of synapsis structure and the expression of cAMP-response element binding protein(CREB) in cortex and hippocampus. Methods Thirty 9-month-old healthy male SMAP8 mice were randomly divided into model group, oleanolic acid group and aricept group, and with 10 rats in each group, while 10 healthy male mice of the same age and species as normal group.Oleanolic acid group and aricept group were given intragastric administration with corresponding drugs, while the normal group and model group were given the same amount of physiological saline. 4 weeks later, the ethology changes were observed by Morris water maze and morphology changes of hippocampus neurons were viewed by electron microscope and the expression of CREB was detected by Western Blot. Results (1)Morris water maze results suggested that compared with the normal group, the latency time in the model group mice was longer, which were ((83.33±4.96) s, (75.13±6.01) s, ( 71.75±7.77) s, (63.40±8.93) s, (60.97±8.38) s), while compared with the model group, the latency time in the oleanolic acid group and the aricept group was remarkably shorter(P<0.05), which were (75.97±4.49)s, (64.98±4.93)s, (64.16±6.23)s, (53.47±5.99)s, (47.91±7.64)s and (71.30±7.65)s, (63.32±7.57)s, (59.82±4.69)s, (52.28±5.90)s, (46.22±7.27)s respectively. In the spatial probe trial, compared with the normal group, the crossing times of the model was less, while compared with the model one, the crossing times of the oleanolic acid group and the aricept group was more(P<0.05). (2)Compared with the normal group, the number of synapses in the model group was smaller, in which the synaptic cleft was mixed with the front of synapses severely swollen, uninform synaptic vesicles and few clear outlines of mitochondrias. While the oleanolic acid group and the aricept group had clear synapses outlines with the front of synapses slightly swollen, intensive and uniform synaptic vesicles and clear mitochondrias with their cristae not easy to be seen. (3)The Western Blot showed that compared with the normal group, there was a decline in the CREB expression both in the cortex and hippocampus in the model group, while compared with the model group, there was a rise in the oleanolic acid group as well as the aricept group(P<0.05). Conclusion Oleanolic acid can improve the learning and memorizing of model rats, which is possibly related to the increased expression of CREB protein to protect the synapses structure of model mice. Key words: Oleanolic acid; Alzheimer's Disease; SAMP8 mice; Synapsis electron microscope; cAMP-response element binding protein