Lastly, in a very recent in vivo study, administration of the PDE-4 inhibitor FFM reversed cognitive deficits in a transgenic AD mouse model by increasing CREB phosphorylation and BDNF levels and reducing inducible NO synthase (iNOS), TNF-α and IL-1β levels (Guo et al., 2017). The gene discussed is NOS2; the disease is Alzheimer disease.