A rat model of fetal alcohol syndrome: Molecular and behavioral analysis

The maternal consumption of alcohol during pregnancy produces a wide range of abnormalities in the offspring. The main purpose of this thesis is to investigate the (1) effects of prenatal ethanol exposure in two types of animal behavioral models and (2) effects on gene expression patterns produced by prenatal ethanol exposure. Sprague-Dawley rats from fetal alcohol exposure (FAE) and pair-fed (PF) treatment groups were tested as young adults.The purpose of the first study is to assess the effects of prenatal ethanol exposure on anxiety and social behaviors. The elevated plus maze model is used to measure anxiety and the social interaction model is used to study social activity in an open-field. Based on previous literature, we hypothesize that prenatal ethanol exposure will result in a significant difference in activity on the elevated plus maze and open-field. However, our data from the behavioral tests do not show a robust difference between the prenatally exposed and the pair-fed animals. There are no significant effects of prenatal ethanol exposure on the open versus closed arms of the plus maze. There are also no significant effects of prenatal ethanol exposure on social interaction with a companion rat. A reason for the subtle differences between the two behavioral tests is likely due to handling prior to the testing manipulations.The purpose of the second study is to see the effects of prenatal ethanol exposure on gene expression. We hypothesize that FAE significantly affects gene expression, and using gene profiling techniques, we examine the patterns of gene expression in control and treated populations. In our study, we analyze gene expression profiles with pathway analysis as the approach. We identify specific molecular pathways that are significantly impacted by prenatal alcohol exposure. We further extend this study by focusing on the long-term potentiation (LTP) pathway and examine multiple molecular components in this pathway for their gene expression levels. LTP has long been known to be the mechanism by which memories are formed and stored. According to our study, it is compelling to say that FAE can cause profound and long-lasting alterations in the cellular signaling mechanisms associated with activity-dependent synaptic plasticity and memory formation. Our gene expression data also indicate an opposing pattern of ethanol effect on LTP pathway in the hippocampus and hypothalamus.