Interactive effects of prenatal ethanol and N?3 fatty acid supplementation on brain development in mice

This study assesses the combined effects on brain and behavioral development of ethanol administration and supplementation of the maternal diet with long chain n−3 polyunsaturated fatty acids. From day 7 to 17 of gestation, pregnant mice were fed equivalent daily amounts of isocaloric liquid diets; 20% of the energy was provided by either ethanol or maltose-dextrin, and a further 20% by either safflower oil (rich in linoleic acid, 18∶2n−6), or a combination of safflower oil with a fish oil concentrate (rich in eicosapentaenoic acid, 20∶5n−3, and docosahexaenoic acid, 22∶6n−3). On day 18 the liquid diets were replaced by lab chow; a fifth group was maintained on lab chow throughout the experiment. Measures on the pups included brain weight and the fatty acid composition of the brain phospholipids on days 22 and 32 post-conception (birth=day 19), as well as behavioral development. Maternal weight gain during gestation was decreased by ethanol relative to maltose-dextrin, and increased by fish relative to safflower oil. On day 32, the brain weight of ethanoltreated animals fed fish oil was greater than their safflower oil controls, whereas the reverse was true in the two maltose-dextrin groups; a similar trend was apparent on day 22. The brain phospholipid content of the longer chain fatty acids (20∶4n−6, 22∶4n−6, 22∶5n−6, 20∶5n−3, 22∶5n−3, 22∶6n−3) on day 22 reflected that of the prenatal diet, with the proportion of n−3 compounds being higher and that of n−6 floer in the fish oil than safflower oil groups. Prenatal dietary effects were absent by day 32, with the exception of lower 22∶5n−6 in fish oil groups. Dietary supplementation with n−3 fatty acids increased the ratio of 20∶3n−6 to 20∶4n−6, which is consistent with a blockade of the activity of Δ-5 desaturase. On day 22 the incorporation of dietary long chain n−3 fatty acids into the brain phosphatidylcholine fraction was enhanced in the ethanol-treated animals; by day 32 the animals treated prenatally with ethanol also showed increased levels of long chain n−6 compounds. Behavioral development was retarded by ethanol, but there was no effect of the dietary oils. These results support the hypothesis that effects of ethanol on the developing brain may be modified by the availability of an exogenous supply of long chain fatty acids.