UC Berkeley

In mammals, the suprachiasmatic nucleus (SCN) acts as the master circadian pacemaker of the body. The SCN coordinate the thousands of individual oscillators throughout the body to maintain optimal health and homeostatic functioning. The importance of maintaining circadian rhythmicity is exemplified by its role in reproduction, as disruption of the circadian clock inhibits reproduction. Experiment 1 shows that the proper temporal coordination by the SCN of two hypothalamic neuropeptides, GnRH and RFRP-3, is imperative to initiation of the luteinizing hormone (LH) surge that stimulates ovulation in the Syrian hamster. The maintenance of temporal homeostasis in reproductive, neural, and immune health was further studied using a model of circadian disruption similar to chronic jet lag that resulted in an incongruence between the endogenous ~24-hour rhythm generated by the SCN and the environmental 24-hour day. In Experiment 2, jet-lagged hamsters exposed to 6-hour shifts in the light:dark cycle every 3 days for 25 days exhibit a dysregulation in the temporal activation of the GnRH and kisspeptin systems, two neuropeptide populations that stimulate the LH surge, and in the temporal deactivation of the RFRP-3 system that inhibits the reproductive axis, around the time of the LH surge. The importance of temporal homeostasis was further explored in Experiment 3, in which jet-lagged hamsters exhibit decreases in hippocampal cell proliferation and neurogenesis compared to non-jet-lagged controls. Interestingly, jet lag hamsters not only exhibit deficits in learning and memory during the period of repeated phase shifts, but also one month following the cessation of chronic jet lag, suggesting that the jet-lag-induced decrease in neurogenesis has long lasting effects on hippocampal function. Similarly, as jet lag influences hippocampal cell proliferation, it is also shown to impact immune function by dysregulating splenocyte proliferation in Experiment 4. Additionally, both innate and humoral immune functions, including complement system activity, total antibody production, and bacterial killing, are suppressed in jet-lagged hamsters compared to controls. Taken together, the previous studies strongly implicate the necessity of coordination between an intact circadian system and environmental cues to maintain proper homeostatic function.