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 自年中以来被认为是一个相当大的临床问题 70年代的S。由此产生的胎儿的标志性特征之一 酒精综合征是一种中枢神经系统功能障碍， 因此，人们对这种效应进行了大量的实验研究。 酒精对神经细胞发育的影响。然而，它的潜在影响是 酒精对中枢神经系统神经胶质细胞发育的影响及其调控 还没有得到很好的研究。我们之前已经证明，在一只动物身上 发育过程中酒精暴露的Fas模型：延迟 获得髓鞘和产生髓鞘的少突胶质细胞； 会导致髓鞘厚度的永久性减少；并且，会导致 星形胶质细胞数量和范围的增加(胶质细胞增多症)。为了 了解这种改变所涉及的细胞事件，有一个 需要定义在这些时间发生的周期。这项建议 项目是一种光镜下的免疫细胞化学和电子动物 专为定位临时漏洞而设计的模型 参与髓鞘疾病产生的细胞事件和 发育期酒精暴露引起的神经胶质细胞增多症。生产出这样的产品 暴露后，人工饲养的大鼠将提供胃造瘘口饲料。 在出生后的特定阶段中含有高剂量的酒精 与人类妊娠晚期的时间相对应的发育 大脑发育。控制动物将包括人工饲养的动物 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 流食到人工饲养的第1-10天，会产生足足三个 三个月的当量暴露。视神经和脊髓组织将 被取出并准备用于免疫细胞化学和电子显微镜 从出生15天和90天的动物身上。视神经组织将会 研究以确定这种酒精暴露对人体的具体影响 神经胶质细胞系的发育和成熟，髓鞘和 血管限制膜。将对脊髓组织进行检查以 两种来源不同的背柱神经纤维束的对比 发育时间(皮质脊髓和一般感觉束)，如 以及验证在更典型的中枢神经系统区域的视神经发现。

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.