The Effect Of Memantine On Cognitive Functions And The Expression Of Ck2α Hippocampus Of Alzheimer’s Disease Rats Indeced By Aβ_25-35

ObjectiveAlzheimer’s disease is the most common degenerative disease of the central nervoussystem, pathological changes are mainly neurofibrillary tangles (NFT), senile plaqueformation (SP)，and neuron loss. The pathogenesis of AD is complex; so far its cause isunclear, since in the1980s, forming a lot of hypotheses, now widely accepted hypothesis isthat β-amyloid protein hypothesis, the main composition of SP is Aβ. Recent studiesshowed that Aβ can also lead to the abnormal expression of intracellular protein kinaseCK2, thus affecting the function of FAT. Memantine, an uncompetitive NMDA receptorantagonist used for the treatment of Alzheimer’s disease (AD), has been hypothesized tohave neuroprotective properties.The AD models were established by injecting Aβ25-35into the bilateral hippocampusof rats and memantine was administrated. We observe the change of the capability oflearning and memory in Morris water maze, and pathological changes of hippocampus andthe expression of protein kinase CK2α through the methods of HE staining、Nissl staining、Western Blot, for exploring the mechanism of cognitive impairment in AD model rats.MethodsWe establish AD model rats by injecting Aβ25-35into the bilateral hippocampus ofrats.48male healthy Wistar ratsweighing250g-300g, were randomly divided into fourgroups: sham group(SHAM group）,AD model group(AD group), memantine high dosegroup(MEN-H group), memantine low dose group(MEN-L group）. Aβ25-35was dissolvedin0.9%NS to the concentration of2μg/μl and the solution was incubated at37℃for7daysbefore use.2.5μl of Aβ25-35was injected into bilateral hippocampus of rats in AD groupand MEN-H group and MEN-L group, which was performed on a steretaxic apparatus.2.5μl of0.9%NS was injected into bilateral hippocampus of rats in SHAM group. The rats in MEN-H group and MEN-L group was injected intraperitoneally with memantine and0.9%NS for the other two groups.9days later, each group was trained by Morris waterMaze for5days and the results were recorded, After Morris water Maze test, anaesthesiaand perfusion, the rats were killed and the hippocampus were removed for tests. HEstaining and Nissl staining were observed in the structure of neural cells in thehippocampus, western blot detects the expression of protein kinase CK2α.Result(1)the water maze experiment results: AD group, MEN-H group compared withSHAM group had significant increase in escape latency, the time ratio was significantlydecreased and significantly decreased times of through the platform (all P<0.05); theMEN-L group compared with AD group had significant decrease in escape latency,significant decrease times of crossing the platform and the time ratio was significantlyincreased (all P<0.05); SHAM group compared with MEN-L group had no significantdifference in the times of times through the platform, the escape latency, the time ratio,（2）HE and Nissl staining show a clear structure of hippocampus neurons in theSHAM group. The cell nucleus structure is normal. The Nissl’s bodies in theintracytoplasm were abundant. The chromatins of cell nucleus were distributes equally.Hippocampus neurons of Alzheimer’s disease rat were injured. Swelled neurons andbroken neurons were observed and they ranked chaos in the sections. The Nissl’s bodies inthe intracytoplasm and survival neurons were reduced. The structure of hippocampus inMEN-H group and MEN-L group were similar as SHAM group.(3)WB results: AD group compared with SHAM group, the expression of proteinkinase CK2α increased significantly (P<0.05), MEN-H group and MEN-L group in theexpression of protein kinase CK2α compared with AD group was decreased (P<0.05), butcompared with SHAM group, MEN-H group and MEN-L group expression in proteinkinase CK2α increased obviously (P<0.05).Conclusion(1) Infusion Aβ25-35into the bilateral hippocampus can be successfully established theanimal model of AD;(2) Aβ25-35oligomers can lead to nerve cell damage, apoptosis and increase theexpression of protein kinase CK2α, resulting in learning and memory impairment in rats;(3)Memantine intervention can improve learning and memory dysfunction inducedby Aβ25-35in rat model of AD, which may be associated with reduced the expression ofprotein kinase CK2.