Aging alters light- and PACAP-induced cAMP accumulation in the suprachiasmatic nucleus of female rats

Abstract

Light-induced release of pituitary adenylate cyclase activating peptide (PACAP) from retinal ganglion cells can modulate the phase-shifting effects of light though a cAMP-mediated mechanism in neurons of the suprachiasmatic nucleus (SCN). Since older animals (12 months or older) show a reduced behavioral and cellular response to light presented during the early portion of the dark phase of the cycle, we hypothesized that aging may alter the ability of PACAP and cAMP to modulate the phase shifting effects of light. In Expt. 1, we examined basal and light-induced cAMP accumulation at zeitgeber time 14 (ZT14 where ZT0 is the time of lights on). Light exposure resulted in a significant increase in cAMP accumulation in SCN tissue collected from young, but not middle-aged animals. The failure to see an increase in cAMP accumulation in the SCN of middle-aged animals may be related to the fact that basal levels of cAMP were elevated in the SCN of these animals at ZT14. In Expt. 2, we used an in vitro slice preparation of the SCN to determine if aging altered the ability of PACAP to stimulate cAMP accumulation in the SCN at ZT14. PACAP stimulated cAMP in the SCN of both young and middle-aged animals. However, PACAP-induced cAMP accumulation was lower in the SCN of middle-aged animals. Based on these results, we conclude that age-related changes in the responsiveness of the SCN to light input are due to: (1) changes in other input pathways capable of modulating cAMP, and (2) decreases in PACAP receptors in SCN neurons.