NOS2 and Cowden disease: Studies using animal models of chemically-induced CD have revealed changes in the excitability and behavior of the central nervous system, such as activation of hippocampal microglia, changes in glutamate transmission and neuronal plasticity, increased levels of TNF-α, inducible nitric oxide synthase (iNOS), and nitrites in the hippocampus (Riazi et al., 2008; Heydarpour et al., 2016), and declined neuronal regeneration (Riazi et al., 2015; Zonis et al., 2015).