Prenatal alcohol exposure alters expression of genes involved in cell adhesion, immune response, and toxin metabolism in adolescent rat hippocampus

Abstract

Prenatal alcohol exposure can result in mild to severe consequences for children throughout their lives, with this range of symptoms referred to as Fetal Alcohol Spectrum Disorders (FASD). These consequences are thought to be linked to changes in gene expression and transcriptional programming in the brain, but the identity of those changes, and how they persist into adolescence are unclear. In this study, we isolated RNA from the hippocampus of adolescent rats exposed to ethanol during prenatal development and compared gene expression to controls. Exposure to ethanol caused widespread downregulation of many genes as compared to control rats. Gene ontology analysis demonstrated that affected pathways included cell adhesion, toxin metabolism, and immune responses. Interestingly, these differences were not strongly affected by sex. Furthermore, these changes were consistent when comparing ethanol-exposed rats to pair-fed controls provided with a liquid diet and those fed ad libitum on a standard chow diet. We conclude from this study that changes in genetic architecture and the resulting neuronal connectivity after prenatal exposure to alcohol continue through adolescent development. Further research into the consequences of specific gene expression changes on neural and behavioral changes will be vital to our understanding of the FASD spectrum of diseases. AUTHOR SUMMARYAlcohol exposure during fetal development is associated with a wide range of behavioral and physical symptoms that can be observed from childhood throughout adolescence and beyond. It is believed that this exposure may alter gene expression patterns permanently by changing genomic architecture, but the actual changes themselves are still unclear. In this study we examined gene expression patterns in rats whose mothers were given ethanol during their pregnancies. These were compared to control rats whose mothers were fed a similar liquid diet without ethanol as well as rats fed a normal diet. We identified the top differentially expressed genes and performed gene ontology analysis to identify both genes and pathways important in the response to ethanol during fetal development. We focused on adolescent rats since prenatal alcohol exposure has been shown at this stage to influence behavior. We indeed found a number of significant changes in gene expression, suggesting that prenatal alcohol exposure has ongoing consequences throughout and likely beyond adolescence into adulthood. Pathways such as cell adhesion, immune response, and toxin response were all highlighted. Future work will focus on making connections between these gene expression changes and behavioral changes observed at this same life stage.