| With the continuous development of the aging of the global society,Alzheimer ’s disease(AD)is getting more and more attention.According to the "Global Alzheimer’s Disease Report 2016" released by the International AD Association(Alzheimer’s Disease International),the number of people suffering from Alzheimer’s disease in the world is as high as 47 million in 2016,and by 2050,it will nearly triple to 1.32 Billion peopleSome researchers believe that synaptic dysfunction is the initiating factor that causes cognitive impairment in AD.In addition to synaptic loss,synaptic dysfunction and impaired synaptic plasticity are also the main features of cognitive decline in AD.Synaptic plasticity is divided into synaptic structural plasticity and synaptic functional plasticity.Its functional plasticity mainly depends on the activity of related glutamate receptors and the activation of its signaling pathway.Synaptic plasticity-related proteins mainly act on NMDA receptors and AMPA Receptor pathway part.Therefore,synaptic plasticity plays an important role in cognitive function and AD developmentClinical studies have shown that TCM acupuncture has a better effect on dementia,and patients’ daily life and cognitive ability have been improved to a certain extent.Animal experiments have also found that acupuncture can improve synaptic transmission efficiency,synaptic ultrastructure and learning and memory ability in animal models of dementia.This experiment expects to further explore the mechanism of electroacupuncture improving AD cognitive function from the perspective of synaptic plasticityObjectiveUsing APP/PS1 double transgenic mice as animal models,the effects of electroacupuncture intervention on the expression levels of synaptic plasticity-related proteins PSD-95,SYN and GluN2B were observed.From the perspective of synaptic plasticity-related protein expression,the mechanism of electroacupuncture to improve its cognitive function in the early stage of AD pathology was discussedMethodsTwelve male amyloid-protein precursor(APP)/γ-secretase(PS1)double transgenic AD mice were randomly and equally divided into electroacupuncture(EA)group and model group,and other 6 male C57BL/6 mice were used as the normal group.EA(1 Hz/50 Hz)was applied to Baihui(GV20)and bilateral Yongquan(KIl)for 15 min,three times per week for 6 weeks-Intervene every Tuesday,Thursday and Saturday.Immunohistochemistry was used to observe the positive expression of postsynaptic density-95(PSD-95)and SYN.Immunofluorescence observation of Aβ expression.Western blot was used to detect the expression of PSD-95,SYN and GluN2B in the hippocampus.ResultsInmunohistochemical results:PSD-95 positive expression was brown-yellow,mainly distributed on the cytoplasm,membrane and protrusions.In the normal group,the positive expression was darker in color,and the neurites had more expression.The positive expression in the model group was significantly less,lightly colored,and rarely distributed on the protrusions.Compared with the model group,the positive expression of the electroacupuncture group was more denser and darker.The positive expression of SYN was brown-yellow,mainly distributed outside the neurons,and the neuron cell body,axon and dendrite were not marked,and the positive expression difference between the groups was not obvious.However,the positive expression color of the model group was lighter than that of the normal group,and the color of the positive expression of the electroacupuncture group was darker than that of the model group.Compared with the model group,the bulge structure of the normal group is complete and the distribution is continuous and regular,while the morphology structure of the bulge of the model group is incomplete.The bulge structure of the electroacupuncture group is more complete and more regular and continuous than the model group.Immunofluorescence results:Immunofluorescence results showed that 5-month-old APP/PS1 double transgenic mice had already expressed A(3 in the hippocampus,but no senile plaques were observed.There was no expression of Aβ in the brain of normal mice.In the normal group,the nerve cells of the hippocampus are neatly arranged,the nuclei are clear,mainly round or elliptical,and the number is large;while the arrangement of the neurons in the model group is scattered and the nuclei are not clear;compared with the model group,the nerve cells in the electroacupuncture group The rules are more regular and the nucleus is clearer.Western Blot results:Compared with the normal group,the expression level of PSD-95 in the hippocampus of the model group decreased,and the difference was statistically significant(P<0.05);compared with the model group,the expression level of PSD-95 in the electroacupuncture group increased,and the difference was statistically significant(P<0.05).).Compared with the normal group,the expression level of SYN in the model group decreased and the difference was statistically significant(P<0.01);compared with the model group,the expression level of SYN in the electroacupuncture group increased and the difference was statistically significant(P<0.01).Compared with the normal group,the expression level of GluN2B in the hippocampus of the model group decreased and the difference was statistically significant(P<0.01);compared with the model group,the expression level of GluN2B in the electroacupuncture group increased,and the difference was statistically significant(P<0.05)ConclusionElectroacupuncture can increase the levels of synaptic plasticity-related proteins PSD-95,GluN2B,and SYN in hippocampus of pre-pathological APP/PS1 double transgenic mice Improving synaptic plasticity may be one of the mechanisms of electroacupuncture to improve AD cognitive function. |
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