Forebrain hypoplasia following acute prenatal ethanol exposure: quantitative analysis of effects on specific...

The effects of acute prenatal exposure to ethanol on the volumes and neuronal populations of selected forebrain nuclei of postnatal animals have been examined in a mouse model. Pregnant mice were exposed to ethanol (25% ethanol, either two doses at 0.015 ml/g separated by 4 hrs, or a single dose at 0.03 ml/g) on the 8th gestational day and the cytoarchitecture of the basal forebrain, paleo- and neocortex examined quantitatively at P15. Significant reductions in the volume and total number of neurons of ventromedial and central forebrain structures, such as the olfactory bulb, septal nuclei, diagonal band nuclei and caudatoputamen, were observed in mice exposed to the divided ethanol dose, but not following the single dose. The neocortex and primary olfactory cortex were also reduced in volume in offspring exposed to the divided ethanol dose. However increased neuronal density in some neocortical regions of ethanol-exposed offspring suggests that the total number of neocortical neurons is not significantly affected by acute ethanol exposure. The findings indicate that pulse exposure to ethanol on a single day of early development causes deficits in neuronal populations of the ventromedial forebrain and caudatoputamen even in offspring without other major malformations. The results also indicate that caution should be exercised in interpreting the significance of nuclear volume reduction in human infants with fetal alcohol syndrome (FAS) in the absence of neuronal density estimates.