HIPPOCAMPAL NEUROTRANSMITTER SYSTEMS IN FETAL ALCOHOLISM

长期学习障碍已被描述为暴露于 子宫内的乙醇。海马体结构，这是一个与 记忆巩固，对产前的影响相当敏感 人和宫内乙醇动物模型中的乙醇暴露 曝光。我们观察到海马区谷氨酸缺乏 母亲摄入适量食物的大鼠子代的神经传递 在整个妊娠过程中摄入大量的酒精。因为海马体 谷氨酸能系统被认为参与记忆的形成，这 缺陷可能会导致后代出现细微的学习障碍， 母亲在怀孕期间摄入适量的乙醇。这个 这项建议的目的是为了更好地了解 孕期酒精诱导的海马谷氨酸受体缺陷 启动对影响基因表达的环境因素的研究 这些致畸作用。 具体目标是： 1.研究孕期酒精暴露对神经化学物质的影响 谷氨酸神经递质和苔藓纤维锌在发育中的标志物 后代。我们将确定神经化学畸胎学表现为 在发育过程中，这些变化会持续到年轻的成年期和 改变的模式是否表明发育迟缓或 永久性赤字。 2.研究胎龄对孕期酒精暴露的影响 神经化学缺陷。我们将确定哪个鼠龄会产生 神经化学畸形学程度最高的后代。 3.研究不同孕期酒精暴露对胎儿健康的影响 海马神经化学。我们将确定最少的天数 所产生的产前酒精暴露：1)统计上最小 2)每种神经化学物质的最大变化 参数。 4.检测母体血液中乙醇浓度(BEC)对 海马神经化学。我们将确定最低的母体BEC 会产生显著的神经化学变化以及最大的变化 这些参数出现在所研究的BEC范围内。 这些研究将提供关于发育表达的更清晰的图景 子代的神经化学缺陷，母亲年龄，酒精的影响 胎儿发育过程中剂量和时间对这些基因表达的影响 神经化学缺陷和更详细的本质理解 这些神经化学变化。最后，这些数据将提供 信息，以便于将来设计其他研究 环境和遗传因素以及可能导致 旨在直接检验有关心力衰竭发病机制的假说的研究(S) 胎儿期酒精对海马区发育的影响。

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.