Xiusanzhen Improving Spatial Learning-memory In Senescence-accelerated Mouse

Objective:Alzheimer's Disease is a central nervous system disease which occurs in the elderly.The main clinical manifestations are decline in learning and memory ability and cognitive impairment.Studies have shown that the "xiusanzhen" can improve the symptoms of AD,but the mechanism of its action is not clear.Therefore,by observing the effect of the"xiusanzhen" intervention on the spatial learning and memory ability of SAMP8 mice.Methods:7 month old male SAMR1 mice(n=10)and SAMP8 mice(n=50)were used as experimental animals.After the SAMP8 mice were removed from the unqualified mice by the open field test and the Morris water maze test,the remaining 45 mice were randomly divided into P8N,P8A and P80 groups,with 15 rats in each group;SAMR1 mice were group R1N(n=10).Mice in group R1N and P8N were fed normally without any intervention.The mice in group P8A were stimulated by "xiusanzhen"(bilateral acupoints of Ying Xiang and Yin Tang),electric acupuncture,parameter is continuous wave,0.3mA,15Hz,10 min,1 times per day for 4 weeks.Mice in group P80 were given eugenol olfactory stimulation for 30min.The spontaneous activity of mice was observed by open field test,and the effect of "xiusanzhen" on the spatial learning and memory ability of SAMP8 mice was observed by Morris water maze.The expression of AP,P-p38,P-tau and SYP in the hippocampus of mice was detected by WB and IF.Results:Part 1 Effects of different intervention methods on learning and memory ability of SAMP8 mice1)In the Morris water maze test,compared with the SAMR1 mouse,the swimming latency and path length before the intervention of the SAMP8 rat was longer and the target quadrant retention time was shorter(P<0.001),indicating spatial learning and memory impairment is existed.After the intervention,the mice in group P8A were compared with the P8N and P80 groups.The swimming latency and path length of the P8A group were significantly shortened(P<0.001),and the stay time of the target quadrant increased significantly(P<0.05).It suggested that the "xiusanzhen" intervention could significantly enhance the spatial learning and memory ability of the P8 mice.Part 2 Effects of different interventions on pathological changes in hippocampus of SAMP8 mice1)The results of immunofluorescence and immunoblotting showed that compared with the R1N group,the expression of A? in the P8N group was more,the activation rate of p38MAPK increased and the content of SYP decreased(P<0.01),but the increase of the phosphorylation of tau protein was not obvious,indicating that the pathological changes in the hippocampus of P8 mice were similar to those in the brain of the AD patients.Compared with the P8N group,the expression of A? and P-p38MAPK in the hippocampus of P8A group decreased,the expression of SYP increased(P<0.01),but the decrease of P-tau was not obvious;the expression of A? in the hippocampus of P80 group decreased and the expression of SYP increased(P<0.01),and the changes of P-p38MAPK and SYP were not obvious.It is suggested that the intervention of "xiusanzhen" can reduce the expression of A? in the hippocampus,inhibit the activation of p38MAPK and increase the content of SYP in the neurons,but the inhibition effect on the highly phosphorylation of tau protein is not obvious;olfactory stimulation can reduce the expression of A?,but the inhibition of p38MAPK activation and the high phosphorylation of tau protein is not obvious.It is concluded that "xiusanzhen" can improve the spatial memory ability of P8 mice and inhibit the expression of A? and p38MAPK in hippocampus and increase the content of SYP.Conclusions:"xiusanzhen" can obviously improve the learning and memory ability of SAMP8 rats.The possible mechanism is to reduce the over expression of A? in the hippocampus,reduce the damage of neurons,promote the regeneration of synapses,and improve the learning and memory function.