ETHANOL AND NEURONAL DEVELOPMENT

描述：(改编自《调查者摘要》)长期 这项研究的目的是鉴定和表征细胞 酒精引起神经元发育变化的潜在机制，以及 评估这些变化在中枢神经系统异常的病因中的作用 与胎儿酒精综合症(FAS)有关。主要神经病理特征 Fas的表达包括神经元形态发生和突触形成的改变。 海马体。最近的研究已经阐明了一些分子和 轴突和突起的不同生长特征的过程 树枝晶，从而为新的实验确定 乙醇破坏神经元发育的机制。它的用途 胚胎大鼠海马区锥体神经元原代培养的研究 是项目目标不可或缺的一部分。这些培养物中的神经元 在模拟的一系列事件中形成轴突、树突和突触 它们在体内的发育。本方案中的实验旨在使用 免疫荧光细胞化学结合定量形态计量学 分析、延时视频显微镜和Fura-2细胞内游离钙 在以下具体目标中进行测量：(1)比较 不同时间乙醇对培养的海马神经元的作用 对于轴突、树突和突触的发育，(2)区分 乙醇直接作用引起的神经元发育变化 乙醇对神经元的影响，或通过以下途径间接影响神经元 星形胶质细胞，(3)决定乙醇对突起生长的影响 包括改变细胞内钙水平的调节。结果是 这些研究将确定过程的中断是否会产生增长和 分子区隔是乙醇研究的一个关键方面 神经发育毒性，并将提供重要的见解 这些行动背后的机制(S)。这些基本知识可以是 期望为提高鉴别诊断和治疗水平提供依据。 受影响的个人。

DESCRIPTION: (Adapted from the Investigator's Abstract) The long term objectives of this research are to identify and characterize the cellular mechanisms underlying ethanol induced changes in neuronal development, and to assess the role of these changes in the etiology of CNS abnormalities associated with Fetal Alcohol Syndrome (FAS). Key neuropathologic features of FAS include altered neuronal morphogenesis and synapse formation in the hippocampus. Recent studies have elucidated some of the molecules and processes responsible for the distinct growth characteristics of axons and dendrites, thus providing the basis for novel experiments to determine the mechanisms underlying ethanol's disruption of neuronal development. The use of primary cultures of embryonic rat hippocampal pyramidal neurons is integral to the objectives of the project. Neurons in these cultures develop axons, dendrites, and synapses in a sequence of events that mimics their development in vivo. Experiments in this proposal are designed to use immunofluorescent cytochemistry coupled with quantitative morphometric analysis, time lapse videomicroscopy, and Fura-2 intracellular free calcium measurements in the following specific aims: (1) Compare the sensitivity of cultured hippocampal neurons exposed to ethanol at different times relative to development of axons, dendrites and synapses, (2) Distinguish whether ethanol induced changes in neuronal development result from direct effects of ethanol on neurons, or indirect effects on neurons mediated by astrocytes, (3) Determine whether ethanol's effects on process outgrowth involve altered regulation of intracellular calcium levels. The results of these studies will establish whether a disruption of process outgrowth and molecular compartmentalization is a key aspect of ethanol's neurodevelopmental toxicity and will provide important insight into the mechanism(s) underlying these actions. This fundamental knowledge can be expected to provide a basis for improving the identification and treatment of affected individuals.