Effects of prenatal alcohol exposure on neural cells in mice

Abstract

Pregnant DBA/1J mice were treated orally with 1.0 or 2.0 g/kg ethanol from days 11–17 of gestation to determine whether ethanol can perturb normal brain development. On gestational day 18 the fetuses were removed and fetal growth parameters were determined. The cerebrums from one group of fetuses were subsequently analyzed for cell number and protein content. The remaining cerebrums were assayed for their ability to grow in an in vitro cell culture system. Prenatal ethanol exposure decreased fetal body and brain weights and crown-rump length. The brain was particularly affected as indicated by a decreased brain: body wt ratio. The percentage of affected and marginally affected fetuses increased in a dose-dependent manner. While the number of cells/brain was unaffected, the number of cells/g cerebrum and the number of cells/mg cerebral protein was increased. Prenatal ethanol exposure decreased the ability of cerebral cells to grow in culture as demonstrated by the reduced plating efficiency and reduced colony size. The data from the present study suggest that ethanol induces a two-fold effect on mouse brain development. First, since the total number of cells/brain was not appreciably affected by prenatal ethanol treatment, it is possible that the reduction in brain size is due to a decreased amount of neuropil. This putative effect on the neuropil was manifested in vitro by decreased colony area. Second, the decreased plating efficiency of cells from brains of affected fetuses suggests that these cells are not functionally normal. These effects may be important in the pathogenesis of central nervous system anomalies associated with the Fetal Alcohol Syndrome.