针刺研究2026，Vol.51Issue(4)：465-473,9.DOI:10.13702/j.1000-0607.20250733
头穴丛刺调节cAMP/PKA/CREB信号通路改善APP/PS1小鼠海马突触可塑性的机制研究
Study on the mechanism of scalp-acupoint cluster puncture in improving hippocampal synaptic plasticity by regulating the cAMP/PKA/CREB signaling pathway in APP/PS1 mice
摘要
Abstract
Objective To observe the effect of scalp-acupoint cluster puncture on hippocampal synaptic plasticity and the activity of cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response element-binding protein(CREB)signaling pathway in APP/PS1 mice,so as to explore its possible mechanism underlying improvement of Alzheimer's disease(AD).Methods Male APP/PS1 transgenic mice were randomly divided into model,acupuncture,and sham acupuncture groups,with 12 mice in each group.In addition,12 male C57BL/6 mice with the same genetic background were used as the control group.The mice of the acupuncture group received cluster-needle stimulation at"Baihui"(GV20)and 2 spots(2 mm to GV20 on the left and right sides),and those of the sham acupuncture group received cluster-needle stimulation at the bilateral hypochondrial non-acupoints.Following insertion,the needles were twisted rapidly for about 1 min,then retained for 30 min in the acupuncture group.The intervention was conducted once a day,for a total of 28 d.The Morris water maze test and Barnes maze test were used to evaluate the mouse's learning-memory and cognitive ability.The immunohistochemical staining was employed to detect amyloid-β(Aβ)deposition in the hippocampus.The Nissl staining was used to observe the changes of the number of neurons in the hippocampal CA1 area.A transmission electron microscopy was employed to observe the ultrastructure of hippocampal synapses.The Golgi staining was used to observe the dendritic spine density of hippocampal neurons.The protein expressions of cAMP,PKA,CREB,phosphorylated(p)-CREB,postsynaptic density protein 95(PSD-95),and synapsin Ⅰ(SYN1)was detected using Western blot.Results Compared with the control group,the model group showed a significant increase in the escape latency of Morris water maze test and the latency to enter the target hole of Barnes maze test and the percentage of Aβ-positive area(P<0.01,P<0.001),and a striking reduction in the number of target platform crossings in the Morris water maze test,residence time in the target quadrant of the escape box and the number of correct hole entries in the Barnes maze test,number of neurons,dendritic spine density,and the expression levels of cAMP,PKA,PSD-95,SYN1 and p-CREB/CREB ratio(P<0.01,P<0.001).After the intervention,both the increase and decrease of the indexes mentioned above were reversed in the acupuncture group(P<0.01,P<0.001),but not in the sham acupuncture group.Morphological results showed irregular shapes and disordered arrangement of the hippocampal neurons with shrunken nucleoli,atrophied mitochondria,broken mitochondrial cristae,decreased synapses and vesicles in the model group,which was relatively milder in the injury degree,for example,increase in the number of synapses and vesicles,relatively complete mitochondrial cristae,etc.,in the acupuncture group.Conclusion Scalp-acupoint cluster puncture can improve the learning-memory ability in APP/PS1 mice,which may be associated with its functions in enhancing the hippocampal synaptic plasticity and up-regulating the cAMP/PKA/CREB signaling.关键词
头穴丛刺/阿尔茨海默病/cAMP/PKA/CREB通路/突触可塑性Key words
Scalp-acupoint cluster puncture/Alzheimer's disease/cAMP/PKA/CREB pathway/Synaptic plasticity引用本文复制引用
高伟,李虹霖,李雪,刘安南,李建辉,叶秋燕,黄颖,杨丰鸽,宋婧,邢丽萍..头穴丛刺调节cAMP/PKA/CREB信号通路改善APP/PS1小鼠海马突触可塑性的机制研究[J].针刺研究,2026,51(4):465-473,9.基金项目
国家自然科学基金项目(No.82105035) （No.82105035）
黑龙江省自然科学基金项目(No.LH2023H064) （No.LH2023H064）
黑龙江省中医药管理局项目(No.ZHY2024-304) （No.ZHY2024-304）
江苏省卫生健康委科研项目(No.Z2024065) （No.Z2024065）
淮安市自然科学联合专项项目(No.HABL202222) （No.HABL202222）
