Psychological stress, such as inescapable foot shocks, social defeat stress, restraint stress, and social isolation, has been shown in multiple rodent models to induce both depression-like behavior and the activation of GSK-3 and NF-κB [39,51,52,53,57,59,137,140], which is likely due to the DAMP-mediated activation of the TLR4 [58,61,62,141]. Here, TLR4 is linked to major depressive disorder.