ALCOHOL-INDUCED EFFECTS IN THE DEVELOPING CNS--GLIAL CELLS AND MYELIN

人类胎儿在怀孕期间接触酒精的情况一直是 被认为是一个相当大的临床关注的问题，因为中期- 70年代 结果胎儿的标志性特征之一 酒精综合征（FAS）是中枢神经系统（CNS）功能障碍， 因此，有许多实验研究的影响， 酒精对神经细胞发育的影响 然而， 酒精对中枢神经系统神经胶质细胞的发育及其发育的影响， 还没有得到很好的研究。 我们之前已经展示过， FAS模型，即发育期暴露于酒精： 髓鞘和产生髓鞘的少突胶质细胞的获得; 可以导致髓鞘厚度的永久性减少;并且，可以导致 星形胶质细胞（胶质细胞增生）的数量和程度增加。 为了 了解这种变化所涉及的细胞事件，有一个 需要定义在这些时间发生的时间段。 这一拟议 项目是一个光镜免疫细胞化学和电子动物 专门设计用于定位时间漏洞的模型， 参与髓鞘疾病产生的细胞事件， 神经胶质增生症。 产生这样 暴露后，将为人工饲养的大鼠提供胃造口术喂养的饲料 在出生后的特定阶段含有高剂量的酒精 与人类第三个三个月期间的时间相对应的发展 大脑发育 对照动物包括人工饲养的 等热量饮食中不含酒精的动物和正常哺乳大鼠 小狗 其他暴露，通过添加受控的产前暴露， 人工饲养第1-10天喂流质饲料，将产生一个完整的三 三个月等效暴露。 视神经和脊髓组织 取出并准备用于免疫细胞化学和电子显微镜检查 15和90日龄的动物。 视神经组织将被 研究以确定这种酒精暴露对 神经胶质细胞谱系、髓磷脂的发育和成熟， 血管界膜 将检查脊髓组织， 对比两个不同来源的背柱神经纤维束， 发育时间（皮质脊髓束和一般感觉束），如 以及验证在更典型的CNS区域中的视神经发现。

The exposure of the human fetus to alcohol during gestation has been recognized as a problem of considerable clinical concern since the mid- '70's. One of the hallmark characteristics of the resultant fetal alcohol syndrome (FAS) is central nervous system (CNS) dysfunction, consequently there have been numerous experimental studies of the effects of alcohol on nerve cell development. However, the potential effects of alcohol on the development of CNS glial cells and their elaborations, have not been as well studied. We have previously shown, in an animal model of FAS, that developmental exposures to alcohol: delay the acquisition of myelin and the oligodendroglial cells that produce myelin; can cause a permanent reduction in myelin thickness; and, can cause an increase in the numbers and extent of astroglia (gliosis). In order to understand the cellular events involved in such alterations, there is a need to define the periods of occur at those times. This proposed project is a light microscopic immunocytochemical and electron animal model designed to specifically localized the temporal vulnerability and cellular events involved in the production of myelin disorders and gliosis due to developmental alcohol exposures. To produce such exposures, artificially reared rats will be provided gastrostomy fed diet containing high doses of alcohol during specific stages of postnatal development that correspond to times during the third trimester of human brain development. Control animals will include artificially reared animals without alcohol in their isocaloric diet and normal nursing rat pups. Other exposures, by adding controlled prenatal exposures with liquid diet to artificial rearing on days 1-10, will produce a full three trimester equivalency exposure. Optic nerve and spinal cord tissues will be removed and prepared for immunocytochemistry and electron microscopy from animals at 15 and 90 days of age. Optic nerve tissue will be studied to determine the specific effects of such an alcohol exposure on the development and maturation of glial cell lineages, myelin, and vascular limiting membranes. Spinal cord tissue will be examined to contrast two dorsal column nerve fiber tracts of differing origin and times of development (the corticospinal and general sensory tracts), as well as to verify optic nerve findings in a more typical CNS area.