| Objective: The purpose of this research project was to define a preferable effect of electroacupuncture(EA)on Alzheimer’s disease(AD)in different stages,and to evaluate how the effects of EA vary in the cognitive function,ultrastructure of neurons and the pathology of β-amyloid protein(Aβ)and microtubule-associated protein tau in SAMP8 mice.Methods: SAMP8 mice were randomly divided into three groups: Model group,3-month-old EA group and 9-month-old EA group;meanwhile SAMR1 mice were treated as Control group.Twelve mice per group.The 3-month-old EA group and 9-month-old EA group were intervened with acupuncture at “Baihui”(GV 20),“Dazhui”(GV 14)and “Shenshu”(BL 23),connect the G6805-Ⅰ EA device with “Dazhui” and “Shenshu”(Bilateral alternation)for 20 minutes per time,2 Hz,1.5~2 mA,once a day,8 days as a course of treatment,with an interval of 2 days,30 days in total.Finally all mice were sacrificed after their learning and memory ability was detected by Morris water maze test in ten-month old.Ultrastructure of hippocampal neurons in mice were observed by Transmission Electron Microscopy(TEM).The expression of Aβ and tau in hippocampal region of mice were detected by immunohistochemistry,whereas the mRNA expression of Aβ and tau in hippocampus was measured by Real-time Quantitative polymerase chain reaction(qPCR).Results:1.Morris Water Maze: ⑴ Place navigation test: Compared with the control group,the escape latency of the Model group was significantly prolonged(P<0.01);compared with the model group,the average escape latency of the EA group was shorter(P<0.05);compared with the 9-month-old EA group,the average escape latency of the 3-month-old EA group was shorter(P<0.05).⑵Spatial probe test: compared with the Control group,the time spent on the original platform quadrant in the model group was shorter(P<0.01)and the number of times crossing the platform was less(P<0.01);compared with the model group,the time spent on the original platform quadrant in the EA group was expanded(P<0.05)and the frequency crossing the platform was increased(P<0.05);compared with the 9-month-old EA group,the In the 3-month-old EA group,the time staying in the platform was extended and the number of crossing platforms was increased(P<0.05).2.TEM: In the Control group,the number of organelles of hippocampal neurons in CA1 area of mice was abundant,the structure of synapses was clear and synaptic vesicles were ample;in the Model group,the synaptic structure of neurons was incomplete,the demarcation of presynaptic and postsynaptic membranes was unclear,and synaptic vesicles were swollen and fewer;compared with the Model group,the number of synapses in the 9-month-old EA group and the 3-month-old EA group was augmented.The synaptic structure of the 3-month-old EA group was clearer and more complete than that of 9-month-old EA group.3.Immunohistochemical: ⑴ Aβ: Compared with the Control group,Aβ in the Model group increased significantly(P<0.01);compared with the Model group,Aβ in the 9-month-old EA group and the 3-month-old EA group decreased significantly(P<0.01),and the 3-month-old EA group reduced more significantly(P<0.05).⑵Tau:(1)Tau-5 was used to detect total Tau in this experiment.Compared with the Control group,Tau-5 in the Model group increased significantly(P<0.01);compared with the Model group,Tau-5 in the 9-month-old EA group and the 3-month-old EA group depressed significantly(P<0.01),while Tau-5 in the 3-month-old EA group was alleviated(P<0.01);(2)p-Tau was detected by AT8 and p-Tau(T231).Compared with 3-month-old EA group,AT8 and p-Tau(T231)were higher in Model group(P<0.01)and 9-month-old EA group(P<0.01);compared with Model group,the positive expression of AT8 and p-Tau(T231)in Control group(P<0.01)was significantly abated.4.Western blot: Compared with the Control group,the expression of Tau-5 and AT8 in the Model group increased significantly(P<0.01).Compared with the Model group,the expression of Tau-5 and AT8 decreased in the 3-month and 9-month-old EA group(P<0.01).Compared with 3-month-old EA group,the expression of Tau-5 and AT8 was higher in 9-month-old EA group(P<0.01).5.qPCR: Compared with the Control group,the expression of Aβ and Tau in the hippocampus of the Model group increased significantly(P<0.01).Compared with Model group,the expression of Aβ and Tau in hippocampus of 3-month-old and 9-month-old EA group decreased(P<0.05).Compared with 3-month-old EA group,the expression of Aβ and Tau in hippocampus of 9-month-old EA group was higher(P<0.05).Conclusion:1.The early(3-month-old)EA intervention of AD could effectively meliorate the learning and memory ability of SAMP8 mice.2.Early EA treatment of AD was more conducive to maintaining the integrity of synaptic structure and increasing the density of synaptic vesicles,thereby improving the synaptic function of neurons.3.EA can,especially intervened in early stage,effectively suppress the aberrant expression of Aβ and tau,meanwhile alleviate tau hyperphosphorylation. |
PDF Full Text Request