EXPERIMENTAL FETAL ALCOHOL SYNDROME

胎儿酒精综合征(Fas)大鼠和胎儿酒精综合征的研究 实验Fas表明，大脑的结构和功能 都会受到产前酒精暴露的深刻影响。乙醇诱导 缺陷包括小脑、大脑皮质变薄和减少。 大脑皮层神经元的数量。这些发现中的每一个都可能导致 原因只有一个--乙醇的毒性作用会导致神经元死亡。 测定中枢神经系统(CNS)中神经元的数量 通过细胞增殖和迁移增加神经元，并通过 由于神经元的死亡而导致的神经元的丧失。我们将检验你的假设 出生前暴露于乙醇会增加大鼠神经细胞的死亡率 发育中的神经系统。将使用三组大鼠：大鼠 会被喂以含酒精的液体饮食，成对喂食等卡路里 液体控制饮食，或喂食食物和水。 在第一个实验中，产前接触乙醇对 大脑皮层神经元死亡将被检查。我们将(A)表演 垂死神经元形态的光镜分析 用单抗、ALZ-50或银染鉴定 技术和(B)使用免疫电子显微镜方法和黄金- 染色超微结构和突触的色调分析技术 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而死亡 在大脑皮质的某一特定部分。此外，我们还将计算 乙醇对ALZ-50阳性、加和、银染色数的影响 染色的、固缩的神经元位于同一皮质节段。(D)我们会 对ALZ-50的时间表达进行生化检测- 免疫反应性。 在第二个实验中，我们将确定其他中枢神经系统结构是否 大脑皮层也受到影响。我们将使用以下方法重复上述大部分研究 三叉神经的主要感觉核。这个 研究PSN的优点是它的结构更简单 包含比皮质和它更同质的神经元群体 是由数不清的神经元组成的。此外，PSN 代表中枢神经系统的病灶和颅面畸形的特点 Fas的。 在第三个实验中，我们将检验乙醇诱导 神经元死亡是由于发育早期发生的改变造成的。 我们将研究酒精对死亡起源时间的影响。 神经元及其迁移与神经元的关系 死亡。我们将研究乙醇对异位存活的影响。 神经元和适当迁移的神经元与细胞外基质 这会影响神经元的迁移。 建议的实验是对Fas和Fas机制的集中研究 中枢神经系统缺陷与Fas相关假说的检验 酒精诱导的神经元死亡增加。

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.