HMOX1 and major depressive disorder: In this study, we utilized a multifaceted approach involving viral HO-1 overexpression in the hippocampus, CO-RM administration in the H2O2-induced cellular injury model, CO-rich saline, or CO gas administration alone or in combination with the LPS model of depression to systematically dissect the therapeutic and neuroprotective role of the HO-1/CO system in depression.