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

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.