Alternating current stimulation promotes neurite outgrowth and plasticity in neurons through activation of the PI3K/AKT signaling pathway  

作　　者：Hao Zhong Cong Xing Mi Zhou Zeyu Jia Song Liu Shibo Zhu Bo Li Hongjiang Yang Hongpeng Ma Liyue Wang Rusen Zhu Zhigang Qu Guangzhi Ning 

机构地区：[1]International Science and Technology Cooperation Base of Spinal Cord Injury,Tianjin Key Laboratory of Spine and Spinal Cord Injury,Department of Orthopedics,Tianjin Medical University General Hospital,Tianjin 300052,China [2]Department of Spine Surgery,Tianjin Union Medical Center,Tianjin 300121,China [3]College of Electronic Information and Automation,Advanced Structural Integrity International Joint Research Center,Tianjin University of Science and Technology,Tianjin 300222,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第11期1718-1729,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Tianjin Key Medical Discipline (Specialty)Construct Project (No.TJYXZDXK-027A);the National Natural Science Foundation of China (Nos.82072439 and 82272470);the Tianjin Health Key Discipline Special Project (No.TJWJ2022XK011);the Basic Research Cooperation Project of Beijing-Tianjin-Hebei (No.20JCZXJC00080).

摘　　要：As a commonly used physical intervention,electrical stimulation(ES)has been demonstrated to be effective in the treatment of central nervous system disorders.Currently,researchers are studying the effects of electrical stimu-lation on individual neurons and neural networks,which are dependent on factors such as stimulation intensity,duration,location,and neuronal properties.However,the exact mechanism of action of electrical stimulation remains unclear.In some cases,repeated or prolonged electrical stimulation can lead to changes in the morphology or function of the neuron.In this study,immunofluorescence staining and Sholl analysis are used to assess changes in the neurite number and axon length to determine the optimal pattern and stimulation parameters of ES for neurons.Neuronal death and plasticity are detected by TUNEL staining and microelectrode array assays,respec-tively.mRNA sequencing and bioinformatics analysis are applied to predict the key targets of the action of ES on neurons,and the identified targets are validated by western blot analysis and qRT-PCR.The effects of alternating current stimulation(ACS)on neurons are more significant than those of direct current stimulation(DCS),and the optimal parameters are 3μA and 20 min.ACS stimulation significantly increases the number of neurites,the length of axons and the spontaneous electrical activity of neurons,significantly elevates the expression of growth-asso-ciated protein-43(GAP-43)without significant changes in the expression of neurotrophic factors.Furthermore,application of PI3K/AKT-specific inhibitors significantly abolishes the beneficial effects of ACS on neurons,con-firming that the PI3K/AKT pathway is an important potential signaling pathway in the action of ACS.

关 键 词：electrical stimulation cortical neurons neural regeneration neurite outgrowth and plasticity alternating current stimulation. 

分 类 号：Q5[生物学—生物化学]