Glymphatic Dysfunction Induced Oxidative Stress and Neuro-Inflammation in Major Depression Disorders

Major Depression disorder (MDD) is a potentially life-threatening mental illness, however, many patients have a poor response to current treatments. Recent studies have suggested that stress- or trauma-induced oxidative stress and inflammation could be important factors involved in the development of MDD, but the mechanisms remain unclear. We showed that the glymphatic system is a recently discovered structure in the brain that may be involved in the clearance of large molecular and cell debris in extracellular space. In addition, the glymphatic system can help with the removal of reactive oxygen species (ROS) and cytokines such as IL-1β and HIF-1α. Glymphatic impairment can lead to ROS accumulation in the microenvironment, inducing cellular injury signaling and activating NLRP3 in microglia to induce inflammation and, thus, many brain diseases, including psychiatric disorders. Therefore, trauma-induced glymphatic impairment could induce oxidative stress and inflammation, and thus MDD. This paper will review recent advances with regard to stress-induced glymphatic system impairment and ROS-mediated inflammation in MDD.