NO-cGMP-PKG pathway in the SCN: the leftovers

PLANO S.A.; CHIESA J.J.; BAIDANOFF F.; AGOSTINO P.V.; DE LA IGLESIA, H.O.; GOLOMBEK D.A.

Huerta Grande, Córdoba

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

Sociedad Argentina de Investigación en Neurociencia

The NO/cGMP/PKG pathway is essential for light synchronization of the circadian clock. PDEs are key regulators of intracellular cGMP concentrations. To study the regulation of cGMP levels in the hamster SCN, we have determined by RT-PCR the presence of several PDEs isoforms in this model. In hamsters receiving specific PDE5 inhibitors, reentrainment to a 6 hr phase advance of the LD cycle took significantly shorter than controls, also elicited an increase in light-induced phase advances when injected 45 min before light stimulation at CT18, and increased the number of PER1-ir cells at CT18. We have studied the role of nitric oxide (NO) in the intercellular communication within the SCN. Administration of the NO scavenger PTIO blocked photic phase advances and inhibited light-induced cFOS and PER1-ir. In addition, we found an inhibition of the non-parametric entrainment to a 23 hr cycle in hamsters receiving a single dose of PTIO before light stimulation. Pharmacological inhibition of PDE5 affects photic entrainment, indicating a potential benefit for circadian disorders which require an increase in light signaling to the clock. These findings could serve as a basis for pharmacological treatment for optimizing circadian adaptation to environmental changes, including jet-lag.