| Maternal consumption of ethanol during pregnancy can produce teratogenic effects in the offspring, including the fetal alcohol syndrome. The brain is a key target of ethanol teratogenesis, in which ethanol can produce neurodegeneration in selected areas, including the hippocampus and cerebellum. However, the time course of neuronal cell loss is not clearly understood. The research objective was to test the hypothesis that chronic prenatal ethanol exposure, via maternal ethanol administration, produces differential time course of loss of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells. Timed pregnant guinea pigs received chronic oral administration of ethanol, isocaloric sucrose/pair feeding, or water throughout gestation (term, about gestational day (GD) 68), and the offspring were studied at GD 62 (near-term fetus), postnatal day (PD) 1 (neonate), PD 5 and PD 12 (early postnatal life). Ethanol treatment, compared with isocaloric-sucrose/pair-feeding and water treatments, decreased brain, hippocampal, and cerebellar weights at GD 62, PD 1, and PD 12. Only brain and hippocampal weights were decreased at PD 5. Hippocampal CA1 pyramidal and cerebellar Purkinje cell numbers were unaffected at GD 62. Ethanol treatment produced about a 25%, 30% and 30% loss of hippocampal CA1 pyramidal cells at PD 1, PD 5 and PD 12, respectively, and about a 30% loss of cerebellar Purkinje cells at PD 12 only. At PD 5, Purkinje cell number remained unaffected by ethanol treatment; however, the number of apoptotic Purkinje cell nuclei doubled, based on detection using the TUNELRTM method. The data demonstrate that chronic prenatal ethanol exposure produces differential time course of loss of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells in the developing guinea pig, involving apparent apoptotic neurodegeneration of the Purkinje cells. |
