Circadian rhythm of cell proliferation in the telencephalic ventricular zone: effect of in utero exposure to ethanol

Abstract

The neocortical ventricular zone is composed of a desynchronized population of proliferating cells. These cells give rise to neurons in the infragranular laminae of neocortex. The present study documents a diurnal rhythmicity of cell proliferation in the ventricular zone and examines the effects of ethanol on this biological clock. Pregnant rats were fed one of 3 diets. They were provided an ethanol-containing (6.7% v/v) liquid diet ad libitum between gestational day (G) 6 and G18, pair-fed an isocalorir liquid control diet, or fed chow and water. Throughout the experiments, the rats were fed either at 08.00 h (E.S.T.) or at 17.00 h (lights on 06.00 to 18.00 h). Rats were given a single injections of bromodeoxyuridine (BrdU) on G17 at one point during a 24 h period (03.00, 06.00, 09.00 h, etc.). The fraction of ventricular cells that incorporated the BrdU was determined using quantitative immunohistochemical methods. Pair-fed control rats (fed at 08.00 or 17.00 h) consumed their food within 4 h of presentation. The ratio of cells passing through the S-phase of the cell cycle changed diurnally; the ratio was highest during the day (0.52 ± 0.01 at 12.00 h) and lowest during the night (0.40 ± 0.02 at 03.00 h). In contrast, the ethanol-fed rats grazed on their food throughout the dark cycle regardless of when the food was presented. The mean peak blood ethanol concentration was 142 ± 13 mg/dl during the dark phase and less than 25 mg/dl during the light phase. Prenatal exposure to ethanol eliminates the fetal circadian rhythm in cell proliferation (mean labeling index of 0.45 ± 0.03). This ethanol-induced alteration demonstrates the resiliency of the developing system; its ability to compensate for traumas that alter the epigenetic control of development.