Hippocampal cell proliferation across the day: increase by running wheel activity, but no effect of sleep and wakefulness

The present study investigated whether proliferation of hippocampal progenitors is subject to circadian modulation. Mice were perfused using 3h intervals throughout the light-dark cycle and brains were stained for Ki-67. Since Ki-67 is not expressed during the G0 phase of the cell cycle, we expected a decline in Ki-67 expression at the moment cells synchronously exit the cell cycle. However, despite the fact that various hippocampal factors fluctuate across the day, the number of dividing cells remained constant. In a second experiment, we studied whether disturbance of normal sleep affected the stable rate in cell proliferation. Our data show that 12h of sleep deprivation during the light phase did not influence proliferating cell number. A third experiment investigated whether physical activity, a condition known to enhance hippocampal cell proliferation, caused an elevation of the steady baseline number of proliferating progenitors, or a peak directly following the active phase of the animals. Mice were housed with a running wheel for 9 days. On the last day, animals were sacrificed either directly before or directly after the active phase. Exercise significantly promoted cell proliferation and this effect appeared to be strongest directly after the active period and to disappear during the resting phase. Our data suggest that hippocampal cell proliferation is not synchronized under basal conditions and is unchanged by sleep deprivation. However, running affected cell proliferation differentially at two times of day. These data demonstrate that the steady rate in cell proliferation is not indispensable, but can be changed by behavioral activity.