GLIOGENESIS, MYELINOGENESIS AND ALCOHOL EXPOSURE

人类胎儿在怀孕期间接触酒精的情况一直是 在过去的十几年里被认为是一个相当大的临床问题 好几年了。尽管人们都知道这一标志之一 由此产生的胎儿酒精综合征(FAS)的特征是中心 神经系统(CNS)功能障碍，出现的相对较少 大鼠中枢神经系统细胞病理的超微结构研究 实验中暴露的动物。酒精引起异常的证据 中枢神经系统中的细胞分化和迁移已被发现 对人类和实验动物的显微研究，以及 在动物中，髓鞘发育的潜在异常已经被注意到。 因为正常的神经胶质细胞成熟是正常神经元所必需的 迁移以及髓鞘的形成，这是一个有趣的研究 发育中的神经胶质细胞和髓鞘，以及神经细胞 动物暴露在酒精中的方式将与 发生在Fas中的暴露时间。这个拟议的项目是一个 神经胶质细胞、髓鞘和神经细胞发育的电子显微镜研究 后来，暴露于酒精的大鼠中枢神经系统中的神经细胞 在这样的模型中。为了与Fas的酒精暴露平行，大鼠将 通过含有35%的母体饮食暴露于怀孕21天 酒精产生的卡路里，然后通过使用进一步暴露于出生后10天 含3%(v/v)乙醇的牛奶日粮。出生后的动物将是 在远离母亲的地方人工饲养，通过 长期植入的胃插管。控制动物将被饲养 来自等热量配对的水坝，通过胃管喂养，但没有 母体或产后饮食中的酒精。动物将被牺牲在 妊娠期、产后期和成熟期的不同时期。 将摘除视神经和脊髓组织，并为 电子显微镜。在研究的第一部分，视神经组织 将进行研究，以确定酒精是否对胶质形成和/或 髓鞘生成。进一步的研究将确定是否对髓鞘有任何影响 而神经胶质细胞会一直持续到成熟。在研究的最后阶段， 从相同的实验动物中发育出的螺旋脐带将被检验 研究神经发生并验证任何视神经发现在更多 典型的中枢神经系统区域。

The exposure of the human fetus to alcohol during gestation has been recognized as a problem of considerable clinical concern for the last dozen years. Although it is well recognized that one of the hallmark characteristics of the resultant fetal alcohol syndrome (FAS) is central nervous system (CNS) dysfunction, there have been relatively few ultrastructural studies of the cellular pathology in the CNS of experimentally exposed animals. Evidence of alcohol induced abnormal cellular differentiation and migration in the CNS have been fund in light microscopic studies of both humans and experimental animals and, in animals, potential abnormalities in myelin development have been noted. Because normal glial cell maturation is necessary for normal neuronal migration as well as myelin formation, it is of interest to examine developing glial cells and myelin, as well as nerve cells in experimental animals exposed to alcohol in a manner which will closely parallel the timing of exposure which occur in FAS. THis proposed project is an electron microscopic study of the development of glial cells, myelin, and later, nerve cells in the central nervous system of rats exposed to alcohol in such a model. To parallel the ethanol exposures of FAS, rats will be exposed for the 21 days of gestation via a maternal diet that contains 35% ethanol derived calories, then further exposed for 10 postnatal days by use of a milk diet containing 3% (v/v) ethanol. Postnatal animals will be artifically reared away from the mothers and the diet administered via chronically implanted gastric cannulas. Control animals will be raised from isocalorically pairfed dams, and fed via gastric cannulas, but without alcohol in the maternal or postnatal diet. Animals will be sacrificed at various times during gestation, during postnatal days, and up to maturity. Optic nerve and spinal cord tissues will be removed and prepared for electron microscopy. In the first portion of the study optic nerve tissue will be studied to determine if alcohol has an effect on gliogenesis and/or myelinogenesis. Further studies will determine if any effects on myelin and glial cells persist into maturity. In the last phase of the study the developing spiral cord from the same experimental animals will be examined to study neurogenesis and to verify any optic nerve findings in a more typical CNS area.