GLIOGENESIS, MYELINOGENESIS, AND ALCOHOL EXPOSURE

胶质生成、髓鞘生成和酒精暴露

• 批准号: 3110589
• 负责人: DWIGHT E PHILLIPS
• 金额: $ 11.81万
• 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 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3110589
• 关键词: blood brain barrier; cell differentiation; cell migration; central nervous system disorders; electron microscopy; embryo /fetus toxicology; ethanol; fetal alcohol syndrome; gestational age; glia; glial fibrillary acidic protein; histopathology; immunocytochemistry; laboratory rat; microscopy; myelin; myelination; optic nerve; spinal cord

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. It has been 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 greatest vulnerability to alcohol and thus, the vulnerability of the particular developmental events known to occur at those times. This proposed project is a light microscopic immunocytochemical and electron microscopic study of the development of myelin and glial cells in the CNS of rats exposed to alcohol in an animal model designed to specifically localize 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 exposed to gastrostomy fed diet containing high doses of alcohol during specific stages of postnatal development in the rat 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.

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， 70年代中期 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，人们对这种影响进行了大量的实验研究 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。 在一个动物模型中， FAS，即酒精的发育暴露：延迟获得 髓磷脂和产生髓磷脂的少突胶质细胞;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（胶质增生）的数量和程度。 为了解 在这种变化中涉及的细胞事件，需要 定义最容易受到酒精影响的时期，因此， 已知发生的特定发育事件的脆弱性 那些时光 这个项目是一个光学显微镜 免疫细胞化学和电镜研究的发展， 暴露于酒精的大鼠中枢神经系统中的髓鞘和神经胶质细胞 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，人工饲养的大鼠将暴露于胃造口术喂养 在出生后的特定阶段，饮食中含有高剂量的酒精 大鼠的发育与第三次 人类大脑发育的三个月。 对照动物包括 人工饲养的动物在其等热量饮食中不含酒精， 正常哺乳期幼鼠。 其他暴露，通过增加控制产前 在第1-10天用流质饮食暴露于人工饲养， 产生一个完整的三个月等效暴露。 视神经和 将取出脊髓组织并准备用于免疫细胞化学 以及15和90日龄动物的电子显微镜检查。视 神经组织将被研究，以确定这样的一个特定的影响， 酒精对胶质细胞发育和成熟的影响 谱系、髓鞘和血管界膜。 脊髓组织 将检查对比两个背柱神经纤维束， 不同的起源和发展时间（皮质脊髓和一般 感觉束），以及验证视神经的发现，在一个更 典型的中枢神经系统区域。