Lai Chunhua, He Weimin, Yang Hua, Lai Junyu, Huang Siyun
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guilin Medical University, Guilin, China.
Neurol Res. 2025 Jun 25:1-16. doi: 10.1080/01616412.2025.2520017.
The safety and effectiveness of electroacupuncture (EA) in treating depression have been scientifically validated. Recent evidence indicates that the c-Jun N-terminal kinase (JNK) pathway is a therapeutic target for anti-depression. This study examines the effects and mechanisms of EA on middle cerebral artery occlusion (MCAO) surgery and chronic-stress-induced post-stroke depression (PSD) mice.
C57BL/6 mice were randomly divided into the sham, MCAO, MCAO+stress, and MCAO+EA+stress groups. After the behavior test, H&E staining was conducted to detect hippocampal changes. TUNEL assay was performed to detect apoptosis. Western blot and RT-PCR were performed to assess the protein levels. Immunohistochemistry was used to detect NF200 and 5-HT expressions.
EA treatment was found to ameliorate depressive behavior in mice by inhibiting neuro-apoptosis and microglia-mediated neuroinflammation. Furthermore, EA protected the hippocampal synaptic plasticity through up-regulating the protein expression of 5-hydroxytryptamine (5-HT), neurofilament-200 (NF-200), postsynaptic density protein 95 (PSD95), synaptophysin (Syn), and brain-derived neurotrophic factor (BDNF), along with increasing the counts of hippocampal synapses. The JNK signaling pathway was continuously activated after MCAO and stress treatments, and EA inhibited the JNK signaling pathway by decreasing the JNK and c-Jun phosphorylation levels and the downstream AP-1 expression.
To summarize, EA effectively suppresses the activation of the JNK signaling pathway, thereby improving PSD-related depressive behavior by enhancing synaptic plasticity and reducing neuro-apoptosis and neuro-inflammation. This study lays a foundation for the clinical application of EA in alleviating PSD-related depressive behaviors, positioning it as a potential alternative therapy for addressing depressive symptoms in PSD.
电针治疗抑郁症的安全性和有效性已得到科学验证。近期证据表明，c-Jun氨基末端激酶（JNK）通路是抗抑郁治疗的靶点。本研究探讨电针对大脑中动脉闭塞（MCAO）手术及慢性应激诱导的脑卒中后抑郁（PSD）小鼠的影响及其机制。
将C57BL/6小鼠随机分为假手术组、MCAO组、MCAO+应激组和MCAO+电针+应激组。行为测试后，进行苏木精-伊红（H&E）染色以检测海马变化。采用TUNEL法检测细胞凋亡。进行蛋白质免疫印迹法和逆转录-聚合酶链反应（RT-PCR）以评估蛋白质水平。采用免疫组织化学法检测神经丝蛋白200（NF200）和5-羟色胺（5-HT）表达。
发现电针治疗可通过抑制神经细胞凋亡和小胶质细胞介导的神经炎症来改善小鼠的抑郁行为。此外，电针通过上调5-羟色胺（5-HT）、神经丝蛋白200（NF-200）、突触后致密蛋白95（PSD95）、突触素（Syn）和脑源性神经营养因子（BDNF）的蛋白表达，以及增加海马突触数量来保护海马突触可塑性。MCAO和应激处理后JNK信号通路持续激活，电针通过降低JNK和c-Jun的磷酸化水平以及下游活化蛋白-1（AP-1）的表达来抑制JNK信号通路。
总之，电针可有效抑制JNK信号通路的激活，从而通过增强突触可塑性、减少神经细胞凋亡和神经炎症来改善与PSD相关的抑郁行为。本研究为电针在缓解与PSD相关的抑郁行为中的临床应用奠定了基础，将其定位为解决PSD抑郁症状的潜在替代疗法。
