Long-term learning disabilities have been described in children exposed to ethanol in utero. The hippocampal formation, a brain region involved with memory consolidation, is quite sensitive to the effects of prenatal ethanol exposure both in humans and animal models of in utero ethanol exposure. We have observed deficits in hippocampal glutamate neurotransmission in rat offspring whose mothers consumed moderate quantities of ethanol throughout gestation. As the hippocampal glutamatergic system is thought to participate in memory formation, this defect may contribute to subtle learning deficits in offspring whose mothers consumed moderate amounts of ethanol during gestation. The objectives of this proposal are to obtain a better understanding of prenatal ethanol-induced hippocampal glutamate receptor deficits and to initiate studies of environmental factors that affect the expression of these teratogenic effects.
The specific aims are to: 1. Examine the effects of prenatal ethanol exposure on neurochemical markers of glutamate neurotransmission and mossy fiber zinc in developing offspring. We will determine what neurochemical teratology is expressed during development, which alterations persist into young adulthood and whether the pattern of alterations suggest developmental delay or permanent deficits. 2. Examine the impact of rat dam age on prenatal ethanol exposure-induced neurochemical deficits. We will determine which rat dam age produces offspring with the greatest degree of neurochemical teratology. 3. Examine the effect of varied periods of prenatal ethanol exposure on hippocampal neurochemistry. We will determine the minimal number of days of prenatal ethanol exposure that produce: 1) the smallest statistically significant changes and 2) the maximal changes in each neurochemical parameter. 4. Examine the effect of maternal blood ethanol concentration (BEC) on hippocampal neurochemistry. We will determine the lowest maternal BEC that produces significant neurochemical alterations and whether maximal changes in these parameters occur within the BEC range studied. These studies will provide a clearer picture of developmental expression of neurochemical defects in offspring, the impact of maternal age, ethanol dose and timing during fetal development on the expression of these neurochemical defects and a more detailed understanding of the nature of these neurochemical alterations. Finally, this data will provide information to facilitate the design of future studies of other environmental and genetic factors along with clues that may lead to studies designed to directly test hypotheses about the mechanism(s) of prenatal ethanol action on developing hippocampal formation.
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