GLIOGENESIS, MYELINOGENESIS AND ALCOHOL EXPOSURE

胶质生成、髓鞘生成和酒精暴露

• 批准号: 3110591
• 负责人: DWIGHT E PHILLIPS
• 金额: $ 7.02万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3110591
• 关键词: alcoholic beverage consumption; cell differentiation; cell migration; central nervous system disorders; electron microscopy; fetal alcohol syndrome; gestational age; glia; histopathology; laboratory rat; myelin; myelination; neurogenesis; optic nerve; spinal cord

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.

人类胎儿在妊娠期间接触酒精的情况已被证实 被认为是最近十几个临床上相当关注的问题 年。 尽管众所周知，其标志之一是 由此产生的胎儿酒精综合症（FAS）的特征是核心 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。 酒精诱发异常的证据 中枢神经系统中的细胞分化和迁移已得到资助 人类和实验动物的显微镜研究 在动物中，髓磷脂发育的潜在异常已被注意到。 因为正常的神经胶质细胞成熟对于正常的神经元来说是必要的 迁移以及髓磷脂形成，有兴趣检查 在实验中发育神经胶质细胞和髓磷脂以及神经细胞 动物接触酒精的方式与 FAS 中发生的暴露时间。 该拟议项目是一个 神经胶质细胞、髓磷脂和神经胶质细胞发育的电子显微镜研究 随后，暴露于酒精的老鼠中枢神经系统的神经细胞 在这样的模型中。 为了平行 FAS 的乙醇暴露，将大鼠 在妊娠 21 天期间通过含有 35% 的母体饮食接触 乙醇产生的热量，然后通过使用进一步接触产后 10 天 含有 3% (v/v) 乙醇的牛奶饮食。 动物产后将 远离母亲的人工饲养和饮食管理 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，通过胃插管喂养，但没有 产妇或产后饮食中的酒精。 动物将被处死 妊娠期间、产后期间以及直至成熟期间的不同时期。 视神经和脊髓组织将被切除并准备好 电子显微镜。 在研究的第一部分中，视神经组织 将进行研究以确定酒精是否对胶质生成有影响和/或 髓磷脂发生。 进一步的研究将确定是否对髓磷脂有任何影响 神经胶质细胞持续成熟。 在研究的最后阶段 将检查同一实验动物正在发育的螺旋索 研究神经发生并验证更多视神经发现 典型的中枢神经系统区域。