EXPERIMENTAL FETAL ALCOHOL SYNDROME

胎儿酒精综合征（FAS）的人和大鼠的研究 FAS实验表明，大脑的结构和功能 都深受产前接触乙醇的影响。 乙醇诱导 缺陷包括小脑畸形，大脑皮层较薄， 皮层神经元的数量。 这些发现都可能导致 原因只有一个--乙醇的毒性作用导致神经元死亡。 确定中枢神经系统（CNS）中神经元的数量 通过细胞增殖和迁移增加神经元， 神经元的死亡所导致的神经元的损失。 我们将检验你的假设， 产前暴露于乙醇会增加胎儿神经元死亡的数量， 发育中的神经系统 将使用三组大鼠： 将喂食含乙醇的液体饮食，成对喂食等热量的 液体对照饮食或喂食食物和水。 在第一个实验中，产前暴露于乙醇对 将检查大脑皮层中的神经元死亡。 我们将（a）执行 对垂死神经元形态的光学显微镜分析 用单克隆抗体、ALZ-50或银染色鉴定 技术和（B）使用免疫电镜方法和金- 染色技术分析染色的超微结构和突触学 神经元 (c)我们将确定神经元的时空序列， 通过记录大脑皮层神经元总数的变化 大脑皮层的特定区域 此外，我们还将计算 乙醇对ALZ-50阳性细胞数、添加量、银- 染色和固缩的神经元在同一皮质段。 (d)我们将 对ALZ-50的时间表达进行生化检查， 免疫反应性。 在第二个实验中，我们将确定其他CNS结构是否 大脑皮层也受到影响 我们将重复上述大部分研究， 三叉神经的主要感觉核（PSN）。 的 研究PSN的优点是它的结构更简单 包含比皮层更均匀的神经元群体， 是由无数个神经元组成的 此外，PSN 代表中枢神经系统和颅面畸形特征的焦点 的FAS。 在第三个实验中，我们将测试乙醇诱导的 神经元死亡是由发育早期发生的变化引起的。 我们将研究乙醇对死亡起源时间的影响 神经元迁移与神经元功能的关系 死亡 我们将研究乙醇对异位妊娠存活的影响。 神经元和适当迁移的神经元和细胞外基质 影响神经元迁移。 拟议的实验是对FAS机制的重点研究， 检验与FAS相关的CNS缺陷导致 酒精引起的神经元死亡的增加。

Studies of human with fetal alcohol syndrome (FAS) and rats with experimental FAS show that the structure and the function of the brain are profoundly affected by prenatal exposure to ethanol. Ethanol-induced defects include microencephaly, a thinner cerebral cortex, and reductions in the number of cortical neurons. Each of these findings may result from a single cause-toxic effects of ethanol that cause neuronal death. The number of neurons in the central nervous system (CNS) is determined by the addition of neurons via cell proliferation and migration and by the loss of neurons due to their death. We will test thy hypothesis that prenatal exposure to ethanol increases the amount of neuronal death in the developing nervous system. Three groups of rats will be used: rats will be fed a liquid ethanol-containing diet, pair-fed an isocaloric liquid control diet, or fed chow and water. In the first experiment, the effect of prenatal exposure to ethanol on neuronal death in cerebral cortex will be examined. We will (a) perform a light microscopic analysis of the morphology of dying neurones identified with a monoclonal antibody, ALZ-50 or a silver staining technique and (b) use an immuno-electron microscopic method and a gold- toning technique to analyze the ultrastructure and synaptology of dying neurons. (c) We will determine the spatiotemporal sequence of neuronal death by documenting the changes in the total number of cortical neurons in a defined segment of cortex. In addition, we will calculate the effects of ethanol on the numbers of ALZ-50-positive, addition, silver- stained, and pyknotic neurons in the same cortical segment. (d) We will perform a biochemical examination of the temporal expression of ALZ-50- immunoreactivity. In the second experiment, we will determine if other CNS structures are affected as is cortex. We will repeat most of the above studies using the principal sensory nucleus of the trigeminal nerve (PSN). The advantage of studying the PSN is that it is a simpler structure containing a more homogeneous population of neurons than cortex and it is composed of a countable number of neurons. Moreover, the PSN represents the focus of CNS and craniofacial malformations characteristic of FAS. In the third experiment, we will test the hypothesis that ethanol-induced neuronal death result from alterations occurring early in development. We will examine the effects of ethanol upon the time of origin of dying neurons and upon the relationship of neuronal migration and neuronal death. We will examine the effects of ethanol on the survival of ectopic neurons and appropriately migrated neurons and the extracellular matrix which impacts on neuronal migration. The proposed experiments are a focussed study into a mechanism of FAS and a test of the hypothesis that the CNS defects associated with FAS result from ethanol-induced increases in neuronal death.