Suprachiasmatic nucleus: NO way

PLANO SA; AGOSTINO PV; CHIESA JJ; BAIDANOFF F; GOLOMBEK DA

Congreso; I Reunion Conjunta de Neurociencias; 2009

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. In hamsters receiving specific PDE5 inhibitors, 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. No differences were observed in either reentrainment rates after a delay in the LD cycle, or light-induced phase delays after a light pulse at CT14. We have also tested natural products containing PDE inhibitors on circadian entrainment. We have studied the role of nitric oxide (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. 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. Preliminary results show an increase of light-induced (50lux) phase advance after the administration of the NO donor NO-Melatonin. 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. These findings could serve as a basis for pharmacological treatment for optimizing circadian adaptation to environmental changes, including transmeridian flight schedules (jet-lag). Also, a role for extracellular NO in the intra-SCN communication is suggested.