Electroacupuncture May Alleviate Depression and Exerts Anti-Inflammatory Effects Through IDO1 Modulation of the Kynurenine Pathway

Depression is one of the most common mental health conditions worldwide. Numerous studies have identified various factors associated with the onset of depression. Among these factors, inflammation is a key contributor. During the inflammatory process, pro-inflammatory cytokines activate indole-2,3-dioxygenase (IDO), which converts tryptophan (TRP) to kynurenine (KYN) via the KYN pathway (KP). This increases the production of neurotoxic byproducts, thereby exacerbating depressive symptoms. Studies have shown that electroacupuncture (EA) has anti-inflammatory and antidepressant properties. The present study aimed to investigate the effects of EA on depression and its mechanisms of action via IDO1 and the KP.

An inflammation-induced depression mouse model was created by injecting lipopolysaccharide (LPS) intraperitoneally. After the model was successfully established, the Hegu (L14) and Taichong (LR3) acupoints were treated with EA at a frequency of 15 Hz and an intensity of 0.3 mA for 45 min. A subset of mice received ketamine as an antidepressant intervention. The following assessments were performed: open-field test (OFT), sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST). An enzyme-linked immunosorbent assay (ELISA) was used to measure IDO1 levels and related inflammatory factors in brain tissue and peripheral blood. High-performance liquid chromatography (HPLC) was used to measure KP metabolism-related metabolite levels. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure IDO1 and inflammation-related factor levels.

LPS significantly induced depression-like behavior in mice. Ketamine effectively alleviated this behavior, exerting an antidepressant effect and suppressing IDO1 expression, as well as the levels of inflammatory factors (IL-1β, TNF-α, and IL-6). Following EA intervention, depression-like behavior in mice with LPS-induced depression was alleviated. EA effectively reduced peripheral and central inflammatory factor expression levels and suppressed IDO1 expression. EA alleviated depressive symptoms in mice by modulating the IDO1-mediated KP.

EA effectively reduced the expression of inflammatory factors, alleviated LPS-induced depressive-like behavior, and improved depressive symptoms by modulating the IDO1-mediated KP.