Interactions between glucocorticoids and the desynchronized circadian system.

Circadian rhythms serve to maintain synchrony between an organism's daily physiological and behavioral functioning and rhythms in the environment. For shift-workers and jet travelers, however, keeping circadian rhythms synchronized to environmental cues presents a challenge. Circadian desynchrony elicits a stress response, and it is likely that stress influences recovery of normal circadian entrainment following a disruption or phase-shift of the light:dark cycle. Taken together with previous research, the data presented herein provide evidence for robust interactions between the circadian and stress systems following a photic phase-shift. Following a 6h phase advance, restraint stress delays reentrainment in both the diurnal degu and the nocturnal rat. Suppressing glucocorticoid synthesis, however, accelerates reentrainment in the degu. A corticosterone (CORT) increase occurs rapidly after exposure to light during the middle of the night, and concomitant restraint exacerbates this increase. These data suggest that the magnitude of the CORT response at the time of a photic phase-shift is likely a mediating factor in reentrainment rate. On a neuroanatomical level, light and restraint have both similar and divergent effects. Light activates the ventrolateral suprachiasmatic nucleus, as defined by an increase in Fos immunoreactivity (-ir). This effect is not altered by the addition of restraint. Within the hypothalamic paraventricular nucleus (PVN), light results in decreased activation of glucocorticoid receptor (GR) containing cells as compared to restraint. The number of Fos and GR positive cells in the posterior paraventricular nucleus of the thalamus is greater following restraint than after exposure to control, light, or light + restraint. It appears that light overwhelms the effect of restraint in the GR-containing cells of this nucleus. Together, these data suggest that light results in less glucocorticoid feedback inhibition than does restraint stress. Knowing that challenges to the circadian system result in increased glucocorticoids may help us to understand and treat the symptoms resulting from disorders with a circadian component. These data have the potential for far-reaching application to the human condition, possibly allowing physicians to identify the etiology of disorders ranging from depression to cancer in patients experiencing repeated challenge to their circadian systems.PhDBiological SciencesNeurosciencesPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125838/2/3224704.pd