ETHANOL AND NEURONAL DEVELOPMENT

描述：（改编自研究者摘要）长期 这项研究的目的是识别和表征细胞 乙醇诱导神经元发育变化的潜在机制，以及 评估这些变化在CNS异常病因学中的作用 胎儿酒精综合征（FAS） 关键神经病理学特征 FAS的改变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， 负责轴突的独特生长特征的过程， 树突，从而提供了新的实验，以确定基础 乙醇破坏神经发育的潜在机制。 使用 原代培养的胚胎大鼠海马锥体神经元， 是项目目标的一部分。 这些培养物中的神经元 轴突、树突和突触在一系列事件中发育， 在体内的发展。 本提案中的实验旨在使用 免疫荧光细胞化学结合定量形态测量 分析、延时视频显微镜和Fura-2细胞内游离钙 （1）比较敏感性， 培养的海马神经元暴露于乙醇的不同时间相对 轴突、树突和突触的发育，（2）区分是否 乙醇诱导的神经元发育变化是直接作用的结果 乙醇对神经元的影响，或对神经元的间接影响， （3）确定乙醇是否对过程生长的影响 涉及细胞内钙水平调节的改变。 的结果 这些研究将确定是否中断的过程生长， 分子区室化是乙醇 神经发育毒性，并将提供重要的见解， 这些行动背后的机制。 这些基本知识可以 预计将为改善识别和治疗提供基础 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.