PTGS2 and major depressive disorder: Estrogen deficiency can cause depression-like behavior, and Huang et al. (44) found in their experiments that estrogen deficiency-induced depression was associated with intestinal flora imbalance and inflammatory response in mice undergoing ovariectomy (OVX), where intestinal flora imbalance caused leaky gut and central inflammation (downregulation of COX-2 expression) to suppress BDNF expression in hippocampal neurogenesis, resulting in depressive behavior in OVX mice.