Neuronal deficits in mice following prenatal exposure to phenobarbital

Pregnant mice (heterogeneous stock) were fed milled food containing 3 g/kg phenobarbital in the acid form (PhB) and water as their only nutritional source from gestation day 9 to 18, with smaller doses on gestation days 6 to 9 and 18 to parturition (B group). Control (C) females received milled food and water. Blood PhB concentrations of females and fetuses were between 40 and 200μg/ml blood. The brains of C and B male offspring were removed at age 50 days, fixed, sectioned, and stained with hematoxylin and eosin. Matching sagittal sections were selected for the study of the cerebellum, hippocampus, and the cerebral cortex. The brain weights of B offspring were 8% smaller than C offspring (P < 0.001). The area of the saggital section of the cerebellar and the hippcampal layers did not differ between groups. There were 30% fewer Purkinje cells in B offspring than in C offspring (P < 0.001). Consequently, their number per square millimeter was 26% smaller (P < 0.01). The number of the hippocamal pyramidal cells was 15% fewer in the B offspring (P < 0.02). There was no difference in the number of granule cells in both the cerebellum and hippocampus. The cerebral cortex was not affected by prenatal phenobarbital administration. The results suggest that the prenatally forming large neurons were affected by phenobarbital administration. However, there was no effect on the subsequent formation of the postnatally developing granule cells.