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 尽管众所周知， 结果胎儿酒精综合征（FAS）的特征是中心 神经系统（CNS）功能障碍，相对较少 中枢神经系统细胞病理学的超微结构研究 实验暴露的动物。 酒精引起的异常证据 已经发现CNS中的细胞分化和迁移 对人类和实验动物的显微镜研究， 在动物中，已经注意到髓磷脂发育的潜在异常。 因为正常的神经胶质细胞成熟是正常神经元细胞发育所必需的， 迁移以及髓鞘形成，这是感兴趣的检查 在实验中， 动物暴露于酒精的方式将密切平行 发生在FA中的暴露时间。 该项目是一个 神经胶质细胞、髓磷脂和 之后，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。 为了平行FAS的乙醇暴露，将大鼠 在怀孕21天内通过母体饮食接触， 37.5%乙醇衍生的卡路里，然后在出生后进一步暴露10天 通过使用含有3%（v/v）乙醇的牛奶饮食。 出生后的动物 人工饲养远离母亲和饮食管理， 长期植入胃插管。 将饲养对照动物 来自等热量配对喂养的母鼠，并通过胃插管喂养，但没有 母亲或产后饮食中的酒精。 动物将在以下时间处死： 在妊娠期间的不同时间，在出生后的日子，直到成熟。 视神经、脊髓、大脑和小脑组织将被切除 并准备用于电子显微镜检查。 视神经组织将被研究 以确定和成熟，并将结果与以前的 仅使用产后暴露的研究。 脊髓组织将被 研究神经元成熟和胶质细胞的发育， 典型的中枢神经系统区域，以验证任何视神经发现。 大脑和/或 小脑组织将被检查，以研究酒精对 神经胶质细胞成熟可影响神经元迁移和成熟。

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. 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 found in light microscopic studies of both humans nad 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 exposures 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 37.5% 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 artificially 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, spinal cord, cerebral, and cerebellar tissues will be removed and prepared for electron microscopy. Optic nerve tissue will be studied to determine and maturation and the results will be compared with previous studies using only postnatal exposures. Spinal cord tissue will be examined to study neuronal maturation and glial development in a more typical CNS area ant to verify any optic nerve findings. Cerebral and/or cerebellar tissues will be examined to study how the effects of alcohol on glial cell maturation may affect neuronal migration and maturation.