| BackgroundAlzheimer's disease(AD),also known as "Senile dementia",is a chronic neurodege-nerative disease characterized by progressive memory,cognitive impairment,behavior and personality changes and so on.Pathological features of AD include senile plaques formed by deposition of A?,neurofibrillary tangles caused by high phosphorylation of tau protein,loss of neurons and so on.According to the World Alzheimer Report 2018,the number of dementia patients increased by 10 million worldwide in 2018,and the total number was about 50 million.By 2030,the number of dementia patients is expected to reach 82 million,and even 152 million by 2050.According to statistics,the total number of AD patients in China has exceeded 6 million,which is the largest number of AD patients in the world.With the aging of the population,the prevalence of AD is also increasing.In addition,the high cost of treatment and care for dementia also impose a heavy burden on society and families.It is estim ated that the global economic expenditure on dementia will be about $1 trillion in 2018,and it is expected to reach $2 trillion by 2030.The pathogenesis of AD has not been fully elucidated.It is believed that the pathogenesis of AD may involves a variety of factors,including abnormal deposition of Ap protein,over phosphorylation of Tau protein,abnormal cholinergic system,synaptic dysfunction,oxidative stress and genetic factors and so on.For different pathogenesis of AD,there are many kinds of AD drugs targeting at the corresponding targets.However,there are only four drugs that ha-ve been widely recognized for the treatment of AD,and instead of completely curing the disease,these drugs can only delay the progress of AD,and may also lead to some adverse effects.Moxibustion,as an important traditional therapy in China,has the effects of disease prevention,health care and preserve longevity.Previous experiments have shown that moxibustion improved the learning and memory ability of AD rats by regulating the level of hippocampal synaptic-related proteins and neurotransmitters,enhancing the expression of neurotrophic factors and their receptors,enhancing the transcription of calmodulin kinase ? in hippocampus,and regulating the signal pathways related to learning and memory,which suggested that the mechanism of moxibustion in treating AD may be related to synaptic plasticity.Therefore,in this experiment,we studied the effects of moxibustion on learning and memory ability,synaptic ultrastructure and synaptic plasticity-related proteins in the hippocampus of SAMP8 mice by taking it as the research subject and moxibustion at Guanyuan acupoint as the intervention to explore the effects of moxibustion on synaptic plasticity of hippocampal neurons in AD mice.ObjectiveTo investigate the effects of moxibustion on learning and memory ability,synaptic ultrastructure of hippocampal neurons of CA1 region and synaptic plasticity-related proteins in SAMP8 mice,exploring the mechanism of moxibustion in the treatment of AD from the perspective of synaptic plasticity.MethodEighteen 6-month-old male SAMP8 mice were randomly and equally divided into two groups,which were used as model and moxibustion group.Nine male SAMR1 of the same age were used as blank group.The mice in blank and model group were grabbed and fixed with fixator every day without any other intervention;the mice in moxibustion group were given moxibustion at Guanyuan point with moxa stick after the same grabbing and fixing.The intervention time of each group was 20 min/d,6 d/week,6 weeks totally.Six weeks later,Morris water maze test was used to test the learning and memory ability of mice in each group.Three mice of each group were randomly selected to observe the synaptic ultrastructure of hippocampal CA1 neurons and measure the parameters of synaptic interface structure.The remaining mice were detected for the expression of synaptophysin(SYN),brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB)and phosphorylated TrkB(p-TrkB)of hippocampus tissue by Western-blot method.Result1.Morris water maze experiment:in the orienteering experiment,the latency of mice in the blank and moxibustion group was significantly lower than that of the model group(P<0.05),but the total swimming distance of mice in each group had no significant difference(P>0.05).In the space exploration experiment,the number of stage-crossing of model group was significantly lower than that of blank group(P<0.05).There was a trend that the number of stage-crossing in the moxibustion group was higher than that in the model group,but there was no significant difference between the two groups(P>0.05);in the blank and moxibustion group,the target quadrant travel ratio was significantly higher than that in the model group(P<0.05);the target quadrant retention time ratio in the blank group was significantly higher than that in the model group,but there was no significant difference between the model and moxibustion group.2.Ultrastructure of synapses in hippocampal CA1 region:compared with the blank group,the synaptic ultrastructure of hippocampal CA1 region was damaged,the curvature of synaptic interface and PSD thickness were significantly reduced,and the synaptic gap was significantly increased in the model group(P<0.05);in moxibustion group,the morphology and structure of synapses were improved under electron microscopy,the PSD thickness was significantly increased and the width of synaptic gap was significantly decreased compared with the model group(P<0.05),but there was no significant difference in the curvature of synaptic interface(P>0.05).3.Synaptic plasticity-related proteins in hippocampus:compared with the blank group,the expression of SYN,BDNF and p-TrkB in hippocampus of mice in the model group decreased significantly(P<0.05).Compared with the model group,the expressions of SYN,BDNF and p-TrkB in hippocampus of mice in the moxibustion group increased significantly(P<0.05).There was no significant difference in the expression of TrkB in hippocampus of mice among the three groups.(P>0.05).Conclusion1.Moxibustion intervention on Guanyuan acupoint of SAMP8 mice can improve learning and memory ability.2.Moxibustion intervation on Guanyuan acupoint of SAMP8 mice can improve the damage of synaptic ultrastructure and the level of synaptic plasticity-related protein in the hippocampus of SAMP8 mice.3.The therapeutic effects of moxibustion on Guanyuan acupoint of SAMP8 mice may be achieved through BDNF/TrkB pathway. |
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