The Study On The Kenpaullone's Memory Dysfunction Impairment In AD Rats Through Methods Of GSK-3/CDK-5

Objective:To acknowledge the Kenpaullone's effect to expressions of GSK-3?,CDK5/p25,P-tau and Synapsin I proteins in region CA3 of Alzheimer's Disease(AD)model rats' hippocampus,preliminary study theKenpaullone'smemory dysfunction impairment and its probable mechanism in AD rat models.Methods:Select 20 SD rats with Morris water maze and randomly divide them into groups of normal comparisongroup,model group,low dosegroup and high dosegroup;inject rats' hippocampus with Wortmannin to create copy models of AD rats,and afterwards inject different concentration of Kenpaulloneto high dose and low dose groups respectively.Verify the learning and memorizing ability of model built rats using Morris water maze 3 weeks after,collect specimens of hippocampus and detect GSK-3?,CDK5/p25,Ptau and protein with immunohistochemistry,Synapsin I with immunoblotting.Results:(1)Every rats selected with Morris water maze before operation could successfully find the hidden platform in a considerably short time and obtains a relatively stable memory capacity.Through hidden platform search experiments 3 weeks after the operation,rats of every group are not found notably differ in swimming speed(P>0.05).Compare rats of model group with normal comparison group,rats of model group have an obvious greater incubation period(P<0.01),times of escape platform passing through and residence time in escape platform obviously decreased(P<0.01),but if compare to high dose group or low dose group,the incubation will greatly shorten(P<0.05)whiletimes of escape platform passing through and residence time in escape platform obviously increased(P<0.05).Taking high dose group compare tonormal comparison group,no remarkable discrepancy is found in incubation period,times of escape platform or residence time in escape platform.(2)The results of phosphorylation for GSK-3?,CDK5/p25 and P-tau protein using immunohistochemistry shows when injected Wortmannin into lateral ventricle,3 kinds of stained positive cells ofGSK-3?,CDK5/p25 and P-tau which are in region CA3 of hippocampus will considerably increase,model group the most among all,followed by low dose group,no statistical significance is indicated(P>0.05),but notably higher than high dose group,normal comparison group,and there is statistically significant(P<0.05 or P<0.01).Meanwhile the two dose group of Kenpaullone,there is statistically significant since GSK-3? and P-tau of low dose group is higher than normal comparison group;there is no significant difference when compare CDK5/p25 for low dose group,GSK-3?,CDK5/p25,P-tau for high dose group to normal comparison group(P>0.05),it indicates Kenpaullone is able to easethe concentration of phosphorylation for GSK-3? and P-tauled by Wortmannin.(3)The results of verification of Synapsin I using immunoblotting indicates when lateral ventricle injected with Wortmannin,the performances of Synapsin I will lower,meanwhile the performances of Synapsin I of high dose group using Kenpaullone are higher than model group,and obvious discrepancy is found(P<0.05).Conclusion:(1)The learning and memorizing ability of AD model rats significantly declined while Kenpaullone would improve it.(2)Kenpaullone can decrease the expressions ofGSK-3?,CDK5/p25 and P-tau protein,and makes Synapsin I protein protected in region CA3 of rats' hippocampus to improve cognitive dysfunction.