Acupuncture Exerts Antidepressant Effects in Rats of Chronic Unpredictable Mild Stress: The Involvement of Inflammation in Amygdala and Brain-Spleen Axis

Abstract Background Acupuncture has shown antidepressant effects in rats with chronic unpredictable mild stress (CUMS). However, the mechanisms of antidepressant effects of acupuncture still need to be explored. In the study, acupuncture was applied to a rat depression model of CUMS, high-mobility group box 1(HMGB1) / toll-like receptor 4 (TLR4) and brain-spleen axis were assessed. Methods Male Sprague Dawley (SD) rats were exposed to CUMS with two stressors per day for 28 days. In the meantime, manual acupuncture (at GV16 and GV23 acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL) were administered daily post-CUMS stressors. Behavioral tests and biological detection methods were conducted in sequence to evaluate depression-like phenotype in rats. Results The results showed CUMS induced depression-like behaviors, hyper-activation of HMGB1/TLR4 signaling pathway, elevated inflammation in amygdala and peripheral blood, and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis. These changes could be reversed by acupuncture to varying extents. Conclusion Acupuncture ameliorated depression-like symptoms induced by CUMS, possibly via regulating inflammation mediated by HMGB1/TLR4 signaling pathway in amygdala and peripheral blood circulation, thus improving behavioral outcomes through brain-spleen axis and HPA axis regulation.