TNF and depressive disorder: These genes include COX-2, matrix metalloproteinase-9, iNOS, interleukin-8 and anti-apoptotic proteins.[54] In a study involving rats subjected to chronic mild and unpredictable stress (CUMS), the animals exhibited depression-like behavior, heightened IDO activity, increased mRNA expression of inflammatory factors (IL-1β, IL-6, TNF-α), activation of the NF-κB signaling pathway, and stimulation of the P2X7R/NLRP3 inflammasome axis, coupled with reduced concentrations of 5-HT in the hippocampus.