HIPPOCAMPAL NEUROTRANSMITTER SYSTEMS IN FETAL ALCOHOLISM

长期的学习障碍已经被描述在儿童暴露于 子宫内的乙醇 海马结构，一个涉及到 记忆巩固，是相当敏感的影响，产前 子宫内乙醇的人类和动物模型中的乙醇暴露 exposure.我们观察到海马谷氨酸盐 神经传递的大鼠后代的母亲消耗适度 在整个妊娠期都有大量的乙醇。作为海马 神经系统被认为参与记忆的形成， 缺陷可能会导致后代的微妙学习缺陷， 母亲在怀孕期间摄入适量的乙醇。的 本建议的目的是更好地了解 产前乙醇诱导的海马谷氨酸受体缺陷， 启动对影响表达的环境因素的研究 这些致畸作用。 具体目标是： 1.检查产前酒精暴露对神经化学的影响 发育中谷氨酸神经传递和苔藓纤维锌的标志物 后代我们将确定神经化学畸形学是如何表达的 在发育过程中，这些变化持续到成年初期， 改变的模式是否表明发育迟缓或 永久性赤字 2.检查大鼠损伤对产前乙醇暴露诱导的 神经化学缺陷我们将确定哪种鼠害产生 神经化学畸形程度最高的后代。 3.检查产前不同时期接触乙醇对胎儿的影响 海马神经化学我们将决定最少的天数 产前酒精暴露产生：1）统计学上最小的 显著变化和2）每种神经化学物质的最大变化 参数. 4.检查母体血液乙醇浓度（BEC）对 海马神经化学我们将确定最低的母亲BEC， 产生显著的神经化学变化， 在这些参数发生在BEC范围内的研究。 这些研究将提供一个更清晰的发展表达的画面 神经化学缺陷的后代，母亲年龄的影响，乙醇 剂量和时间在胎儿发育过程中对这些表达的影响 神经化学缺陷和更详细的了解的性质， 这些神经化学变化。 最后，这些数据将提供 为今后设计其他国家的研究提供资料 环境和遗传因素沿着可能导致 旨在直接检验有关机制假设的研究 产前乙醇对海马结构发育的影响。

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.