Circadian Control of Animal Physiology

We are interested in the mechanisms that generate circadian (~24 hour) cycles of physiology and behavior. Our studies use primarily a Drosophila model, which was invaluable for dissecting molecular mechanisms of the clock, but they also include mammalian models where appropriate. We are interested in the control of behavior by brain clocks and in the control of physiology by brain and peripheral clocks. We recently identified a clock in the Drosophila blood brain barrier (BBB) that confers a 24 hour rhythm on to permeability of the BBB. Specifically, the BBB clock regulates the activity of efflux transporters, such that these transporters pump xenobiotics out of the brain during the day, but are less active at night, thereby increasing BBB permeability at night. The underlying mechanism involves rhythmic expression of gap junctions that serve to maintain 24 hour cycles of magnesium, a positive regulator of efflux transporters, in BBB cells. As many drugs are targets of efflux transporters, we asked if permeability of such drugs is different at different times of day. Indeed, we found that phenytoin/Dilantin has time‐of‐day specific effects in a drosophila seizure model. In recent work, we have characterized rhythms of the BBB in mammalian cells and are addressing the relevant mechanisms. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .