These studies demonstrate the complexity of the negative feedback mechanism of the hippocampus-HPA axis in response to obesity and diabetes-induced hypercorticosteronemia, in which the action of corticosterone on activating inflammasome-associated response and suppressing BDNF signaling induces neuroinflammation and plasticity deficits in the hippocampus (Figure 3). The gene discussed is BDNF; the disease is diabetes mellitus.