GLIOGENESIS, MYELINOGENESIS, AND ALCOHOL EXPOSURE

胶质生成、髓鞘生成和酒精暴露

• 批准号: 2043657
• 负责人: DWIGHT E PHILLIPS
• 金额: $ 11.41万
• 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/2043657
• 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 被认为是一个相当令人担忧的临床问题，因为 70年代中期的S。由此产生的胎儿的特征之一 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。它已经在一种动物模型中显示出来 Fas，发育过程中接触酒精：推迟获得 髓鞘和产生髓鞘的少突胶质细胞；可引起 髓鞘厚度的永久性减少；并且，会导致 星形胶质细胞(胶质细胞增多症)的数量和范围。为了理解 在这种改变中涉及的细胞事件，需要 定义最易受酒精影响的时期，因此， 已知发生在以下地点的特定发育事件的脆弱性 那些时候。这项拟议的项目是一项微不足道的工程。 卵巢癌发生发展的免疫细胞化学和电子显微镜研究 酒精对大鼠中枢神经系统髓鞘和神经胶质细胞的影响 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，人工饲养的大鼠将暴露于胃造口喂养 出生后特定阶段的高剂量酒精饮食 大鼠的发育与第三个时期相对应 人类大脑发育的三个月。控制动物将包括 在等卡路里的饮食中人工饲养不含酒精的动物 正常哺乳的小鼠。其他暴露，通过添加受控产前 在人工饲养的第1-10天，暴露于流质饮食，将 产生足足三个月的等值暴露。视神经和 脊髓组织将被取出并准备进行免疫细胞化学 以及15日龄和90日龄动物的电子显微镜观察。光学 将对神经组织进行研究，以确定这种 酒精暴露对神经胶质细胞发育成熟的影响 谱系、髓鞘和血管限制膜。脊髓组织 将两个背柱神经纤维束进行对比检查 不同的起源和发育时期(皮质脊髓和全身性 感觉束)，以及验证视神经在更多 典型的中枢神经系统区域。