To entrain or not to entrain: The NO-cGMP-PKGpathway in the suprachiasmatic nucleus

CHIESA JJ; PLANO SA; BAIDANOFF F; GOLOMBEK DA

Cordoba

Simposio; Symposium in Signal Transduction and Molecular Medicine; 2010

The NO/GC/cGMP/PKG pathway is essential for photic synchronization of the circadian clock. Phosphodiesterases (PDEs) are key regulators of intracellular cyclic nucleotide concentrations. To study the regulation of cGMP levels in the hamster SCN, we have determined by RT-PCR the presence of PDE5 and other isoforms in this model. In hamsters receiving specific PDE5 inhibitors (sildenafil, vardenafil or taladafil), reentrainment to a 6h phase-advance of the LD cycle took significantly shorter than controls. PDE5 inhibitors also elicited an increase in light-induced phase advances when injected 45 min before light stimulation at CT18. We have studied the role of NO in the intercellular communication within the dorsal and ventral portions of the SCN. Administration of the NO scavenger PTIO blocked photic phase advances and inhibited light-induced cFos-ir, without affecting phase delays. In addition, hamsters receiving a single dose of PTIO before light stimulation show an inhibition in the non-parametric entrainment to 23.5 h cycle and an inhibition of the light-induced Per1-ir. These results demonstrate that pharmacological inhibition of PDE5 affects photic entrainment, indicating a potential benefit for circadian disorders which require an increase in light signaling to the clock.