| ObjectiveTo investigate the effect of saponins from Anemarrhena asphodeloides Bge(SAaB) on the spatial learning and memory ability in aged rats and theexpression of synaptic associated proteins and the mechanisms responsible forthis effect.MethodsForty-five18mon Sprague-Dawley rats, weighting500~600g, wererandomly divided into three groups: aged-control group, the SAaB100mg·kg-1dose group, SAaB200mg·kg-1dose group. The SAaB group rats wereintragastricaly given SAaB of100mg·kg-1, and200mg·kg-1for2months. Thenon-drug-treated control group were intragastricaly given normal saline. Thegroups of young rats (3months, weighting250~350g), as young control group,were intragastricaly given normal saline. After2months, Rats were tested inMorris water maze test, for six consecutive days. After the end of Morris watermaze experiment, some animals were anesthetized and were perfusedtranscardially4%paraformaldelyde solution at4°C for ImmunohistochemicalStaining. The remnant animals in each group were decapitated and the brainswere rapidly removed for Western blot analysis. Immunohistochemical Stainingwas used to investigate the distribution of synaptophysin (SYP) in rathippocampus. Western blot analysis was used to determine the express ofsynaptophysin (SYP), postsynaptic density95(PSD-95), phosphorylatedprotein kinase B (Akt) and phosphorylated mamlian target of rapamycin (mTOR)protein levels. ResultsWe examined the effect of SAaB treatments on learning and memory abilityof aged and young rats for the hidden platform water maze task. In thehidden-platform acquisition training, aged and young rats were abled to find theplatform, as indicated by the decrease in escape latencies and the increasedpercentage of time spent in the target quadrant. But, the aged rats showed onaverage longer time to reach the platform and shorter percentage of time spentin the target quadrant than young rats. Compared with aged control-treated rats,SAaB can significantly improve the learning and memory ability of aged rats,shown by shorter escape latency and increased percentage of time spent in thetarget quadrant. In the probe test, the time spent in the target quadrant of theyoung control group was significantly longer than in the opposite quadrant andthe other two quadrants, but there was no significant difference in the time spentby aged rats in all the four quadrants. The aged SAaB100mg·kg-1and200mg·kg-1-treated groups showed a longer search time in the target quadrant thandid the animals in the aged control group. In aged hippocampus, SYP proteinexpression was lower. Similar levels were seen in regions CA1, CA3anddentate gyrus. The aged SAaB100mg·kg-1and SAaB200mg·kg-1-treatedgroups significantly increased SYP protein expression in CA1region, CA3region and dentate gyrus of hippocampus, compared with the aged controlgroup. The strongest intensity in SYP immunoreactivity was seen in CA3regionof aged SAaB100mg·kg-1and200mg·kg-1-treated groups. Further studiesshowed that expressions of SYP, PSD95, phospho-Akt and phospho-mTORwere decreased in hippocampus of aged-control group(P<0.01), compared withyoung-control group. The treatment with SAaB (100mg·kg-1and200mg·kg-1)showed significant increase in the expressions of PSD95, phospho-Akt andphospho-mTOR in aged rats(P<0.01), compared with aged-control group.ConclusionsThese results suggest that SAaB can obviously improves the spatiallearning and memory ability of aged rats through increasing the SYP andPSD95protein expressions and upregulating Akt/mTOR signaling pathway. |