N-NIitrosomelatonin enhances photic entrainment of the suprachiasmatic circadian clock

BAIDANOFF FM; PLANO SA; DOCTOROVICH F; SUÁREZ SA; GHIRINGHELLI PD; GOLOMBEK DA; CHIESA JJ

Mendoza

Congreso; SAIB; 2012

SAIB

Virtually all physiological processes in mammals are synchronized to the daily light:dark (LD) cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN). Photic stimulation of the retina releases glutamate through the retino-hypothalamic tract; signal transduction of light-induced circadian phase advances is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employed a novel nitric oxide (NO)- donor, N-nitrosomelatonin (NOMel), to enhance photic synchronization of locomotor activity rhythms in hamsters. The intraperitoneal administration of this drug before a sub-saturating light pulse (LP) at circadian time 18 generated a two-fold increase of circadian phase-advances, and also accelerated resynchronization to a 6-hour phase-advance of the LD cycle. However, NOMel had no effect on light-induced circadian phase delays or on resynchronization to a 6-hour delay of the LD cycle. The LP-enhancing effects were correlated with an increased SCN- expression of cFOS. Moreover, in vivo NO release by NOMel was verified by measuring nitrate&nitrite levels in SCN homogenates. Here we demonstrate the chronobiotic properties of NOMel, emphasizing the importance of NO-mediated neurotransmission for circadian phase advances.