Effect of early exposure to ethanol on the protein and DNA contents of specific brain regions in the rat

Abstract

A hallmark of fetal alcohol syndrome is microencephaly. Microencephaly can result from either a reduction in the number of cells, in the amount of neuropil, or both. Inasmuch as CNS structures develop along different time lines, the window of vulnerability to ethanol for each structure may differ. Therefore, the growth of the brain after prenatal exposure to ethanol was compared with that following postnatal ethanol exposure. Rats were exposed to ethanol prenatally (between gestational days 6 and 21 via oral consumption by the pregnant dam) or postnatally (between postnatal days 4 and 12 via intubation). The mean of the daily peak blood ethanol concentration was 146 ± 16 and 127 ± 18 mg/dl for the rats exposed to ethanol pre- or postnatally, respectively. Pair-fed control rats were generated for both the pre- and postnatal conditions. Wet weights, DNA content, and protein content were quantified for 6 brain segments (right and left neocortices, right and left hippocampi, the cerebella, and brainstems) of 21-day-old rats. The total weight of the brain was reduced 12% by pre- or postnatal exposure to ethanol. Only the weights of the neocortex and the cerebellum were significantly reduced by pre- or postnatal treatment. Interestingly, postnatal ethanol exposure increased the weight of the hippocampi. The DNA and protein contents of specific brain segments were affected by ethanol exposure, but all structures were not affected similarly. The greatest effect was on the neocortex; both measures decreased following pre- or postnatal ethanol exposure. The DNA and protein contents of the cerebellum were also affected by pre- or postnatal ethanol exposure. In contrast, while DNA content in the hippocampus was unaffected by prenatal exposure, it was significantly increased by postnatal ethanol exposure. Thus, ethanol-induced microcephaly and differences in DNA and protein content result from changes in cell number and in neuropil volume. These effects, however, differ among CNS structures in a time-dependent manner suggesting that the primary, but not sole target of ethanol is the proliferating cell.