| Background: Alzheimer's disease,also known as "senile dementia",belongs to the category of "dementia" in traditional Chinese medicine.It is a degenerative disease of the central nervous system characterized by progressive cognitive impairment,decline of near-event memory and learning ability.With the acceleration of population aging in China,the number of Alzheimer's disease patients continues to rise,which not only causes serious social problems,but also brings heavy burden to patients' families.AD has become an important threat to the health of the elderly population in China.Although it has been explored for a hundred years,the etiology of AD has not been elucidated.According to the current research,there are more than 30 possible factors and hypotheses of AD.Among them,the two hypotheses about beta-amyloid protein and Tau protein have been the controversial points of the pathogenesis of AD.Chinese medicine has a long history in the treatment of Alzheimer's disease.Acupuncture and moxibustion therapy,as a great treasure of traditional Chinese medicine,is used to treat Alzheimer's disease.It has remarkable effect and unique function advantage.Acupuncture has the overall regulation ability of multi-target,multi-level and multi-channel.Learning and memory impairment,as an important clinical manifestation of AD,is one of the main criteria for early diagnosis of AD.Synaptic plasticity is considered to be the biological basis of the cellular level of learning and memory activities.More and more evidences show that abnormal synaptic plasticity of neurons related to learning and cognitive function plays an important role in the pathogenesis of AD.As a component of mitogen-activated protein kinase(MAPK)signaling system,JNK signaling pathway plays an important role in cell proliferation,apoptosis,synaptic plasticity and neuroinflammation.In our previous study,we found that Dumai electro-acupuncture can reduce the abnormal expression of Abeta and p-tau,improve the cognitive ability and hippocampal neuron loss in AD model mice.However,how does electroacupuncture improve learning and memory? Is the therapeutic effect of electro-acupuncture similar to that of JNK pathway blockers? Is the improvement mechanism related to the changes of synaptic plasticity? This experiment will focus on the above issues.Objective: To observe the possible effect of electro-acupuncture on learning andmemory impairment in AD model mice by using modern science and technology,such as Morris water maze,immunohistochemistry and Western Blot,around the mechanism of synaptic plasticity,and to provide a scientific basis for clinical application of acupuncture therapy to prevent and treat AD.Methods:(1)Intervention therapy: 27 APP/PS1 double transgenic mice were randomly divided into three groups: model group,electro-acupuncture group and drug group;9 C57/BL6 mice of the same age and genetic background were classified as normal group.Nine rats in each group were fed adaptively for one week.In the electro-acupuncture group,"Baihui" and "Yintang" were acupointed with electro-acupuncture,then "Shuigou" was pricked 20 minutes each time,once every other day for 30 days;while in the normal group,model group and drug group(JNK pathway blocker SP600125 was injected intraperitoneally once every other day for 30 days),the same time and intensity of restraint were applied in the electro-acupuncture group to ensure the same experimental conditions,once every other day for 30 days.(2)Behavioral testing: After 30 days,Morris water maze(lasting 6 days)was used to detect the behavioral changes of mice in each group to determine whether the learning and memory impairment occurred in AD model mice,and whether electro-acupuncture therapy could regulate the changes.The effect of JNK pathway blocker SP600125 was observed as a positive control,and the regulatory effect of both groups was evaluated.Generality.(3)Indicator detection: The expression changes of SYP and PSD-95 in hippocampus of four groups of mice were detected by immunohistochemistry and Western Blotting to verify the success of the model and the regulatory role of electro-acupuncture therapy,and to clarify the partial mechanism of electro-acupuncture therapy through affecting synaptic plasticity.Results:(1)From the training results of the water maze experiment,with the increase of training days,the escape latency of mice in each group decreased gradually.Compared with the normal group,the decline trend of the escape latency of the model group was slower;compared with the model group,the decline trend of the escape latency of the drug group and the electro-acupuncture group was more obvious.From the test results,compared with the normal group,the target quadrant swimming time and the number of times crossing the platform in the model group were significantly reduced,while the electro-acupuncture groupand the drug group could significantly inhibit the trend.(2)Immunohistochemical examination showed that compared with the normal group,the gap of neurons in the model group increased,the cell morphology was abnormal,and the expression of PSD-95 was significantly reduced.Compared with the model group,the gap and cell morphology of neurons in the electroacupuncture group and the drug group were significantly improved,and the expression of PSD-95 was significantly increased.(3)Western Blot test showed that the expression of SYP and PSD-95 in model group was significantly lower than that in normal group.Electro-acupuncture group and drug group could significantly inhibit the decrease of PSD-95,but had no significant effect on the expression of SYP.Conclusion:(1)Both electro-acupuncture therapy and drug therapy can improve learning and memory impairment to a certain extent,and exert similar effects;(2)regulating synaptic plasticity in hippocampus may be one of the mechanisms of electro-acupuncture therapy to improve learning and memory impairment in AD model mice;(3)regulating synaptic plasticity in electro-acupuncture therapy may be achieved by inhibiting the expression of PSD-95. |
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