PDE4D and major depressive disorder: In addition to changes in the expression of depression-related or plasticity-related genes (GSK-α, GSK-β, CREB, Arc, COX-2 and NOS1), the behavioral effects of lactate were mediated by an increase in hippocampal p11 (regulator of 5-HT receptors), S100 β (astrocytic marker), Hes5 (transcription vector) and a decrease in cAMP-specific phosphodiesterase-4D (PDE4D) and NOS1 mRNA and protein levels [174].