The Role of VIP in Entrainment of the SCN 

Yan Wang and Erik Herzog

Biology Department, Washington University in St. Louis

 

The circadian rhythm refers to an observed biological activity, such as sleep-awake cycle or gene expression, which oscillates under constant environmental conditions with a period of approximately 24 hours. Repeated phase shift of the rhythm increases the risks of cancer, digestive diseases, and sleep disorders. Located in the hypothalamus, the suprachiasmatic nucleus (SCN) generates and maintains the circadian rhythm. The SCN rhythm is self regulated by the Period2 (PER2) gene through negative feedback loop. The SCN also requires vasoactive intestinal peptide (VIP) to synchronize its individual cellular oscillators. This research is designed to ­­study the role of VIP in entrainment of the SCN. The hypothesis states that VIP changes PER2 expression to synchronize SCN cells. The hypothesis is tested through time dependent and dosage dependent experiments using mouse SCN.

This study demonstrates that the amount of PER2 protein produced varies with not only the timing of VIP treatment but also the concentration of the VIP. In addition the circadian rhythm of PER2 expression is affected by the timing of VIP treatment. VIP causes a phase delay in PER2 expression when given between CT12 and CT18, while producing a phase advance when given between CT18 and CT24.

The ultimate goal is to correlate the acute effect of VIP on PER2 induction with the long term effect of VIP on PER2 phase shift.