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Immunol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aims to investigate the mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a lipopolysaccharide (LPS)-induced acute inflammatory depression model in rats, focusing on the regulation of peripheral pro- and anti-inflammatory cytokines and the effects on the NF-\u03baB signaling pathway in the prefrontal cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A depressive-like behavior model was established via intraperitoneal injection of LPS, and rats were randomly assigned to a normal group, a model group, and a taVNS intervention group. Behavioral assessments included the sucrose preference test (SPT), open field test (OFT), and elevated plus maze test (EPM) to evaluate depressive-like behaviors. Bio-Plex suspension array technology was used to detect inflammatory cytokine levels in serum, and Western blotting was performed to analyze the expression of NF-\u03baB signaling pathway-related proteins in the prefrontal cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Behavioral tests demonstrated that LPS-induced rats exhibited significant depressive-like behaviors, including reduced sucrose preference, decreased activity levels in the open field, and restricted exploratory behavior in the elevated plus maze. taVNS intervention significantly alleviated these depressive-like behaviors. Serum analysis revealed that pro-inflammatory cytokines (e.g., IL-1\u03b2, TNF-\u03b1, MCP-1, IL-18, MIP-1\u03b1, and MIP-3\u03b1) were markedly elevated, while anti-inflammatory cytokines IL-4 and IL-10 were significantly reduced in the model group. taVNS intervention reversed these changes. Western blot analysis showed significant activation of the NF-\u03baB signaling pathway in the model group, characterized by increased p-P65\/P65 and p-I\u03baB\/I\u03baB ratios and elevated TNF-\u03b1 expression. taVNS intervention suppressed excessive activation of the NF-\u03baB pathway by reducing p-P65 and TNF-\u03b1 levels and stabilizing I\u03baB expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that taVNS significantly improves LPS-induced depressive-like behaviors by modulating peripheral pro- and anti-inflammatory cytokine levels and inhibiting the activation of the NF-\u03baB signaling pathway in the prefrontal cortex. These findings highlight the critical role of taVNS in the regulation of the peripheral-central inflammation network and provide theoretical support for the development of taVNS-based non-invasive neuromodulation therapies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1536056","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T04:10:42Z","timestamp":1747368642000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Transcutaneous auricular vagus nerve stimulation alleviates inflammation-induced depression by modulating peripheral-central inflammatory cytokines and the NF-\u03baB pathway in 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