Electroacupuncture improved depressive behaviors and synaptic plasticity of post-stroke depressed mice via inhibiting the JNK signaling pathway.

IF 1.5 4区医学 Q3 CLINICAL NEUROLOGY

Neurological Research Pub Date : 2025-06-25 DOI:10.1080/01616412.2025.2520017

Chunhua Lai, Weimin He, Hua Yang, Junyu Lai, Siyun Huang

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引用次数: 0

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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电针通过抑制JNK信号通路改善脑卒中后抑郁小鼠的抑郁行为和突触可塑性。

目的：对电针治疗抑郁症的安全性和有效性进行了科学验证。最近的证据表明，c-Jun n -末端激酶（JNK）途径是抗抑郁的治疗靶点。本研究探讨了EA对大脑中动脉闭塞（MCAO）手术和慢性应激性脑卒中后抑郁（PSD）小鼠的影响及其机制。方法：将C57BL/6小鼠随机分为假手术组、MCAO组、MCAO+应激组和MCAO+EA+应激组。行为试验结束后，进行H&E染色检测海马变化。TUNEL法检测细胞凋亡。Western blot和RT-PCR检测蛋白水平。免疫组化检测NF200和5-HT的表达。结果：EA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改善小鼠抑郁行为。此外，EA通过上调5-羟色胺（5-HT）、神经丝-200 （NF-200）、突触后密度蛋白95 （PSD95）、突触素（Syn）和脑源性神经营养因子（BDNF）的蛋白表达，增加海马突触数量，从而保护海马突触的可塑性。MCAO和胁迫处理后JNK信号通路持续激活，EA通过降低JNK和c-Jun磷酸化水平及下游AP-1表达抑制JNK信号通路。结论：综上所述，EA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psd相关的抑郁行为。本研究为EA在缓解PSD相关抑郁行为方面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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Research 医学-临床神经学

CiteScore

3.60

自引率

0.00%

发文量

116

审稿时长

5.3 months

期刊介绍： Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.