CHRONIC ETHANOL EFFECTS ON BRAIN GLIAL CELLS

长期酗酒会导致神经心理和大脑损伤， 带来了巨大的医疗和社会成本 很多关于 这些结果集中在乙醇如何影响神经元， 明确偏向于以下概念：1）乙醇直接， 对神经元有特异性毒性，2）神经元病理学解释了 神经心理学缺陷 不管前者是否属实 对于生理乙醇浓度， 神经胶质细胞的复杂性，以及它们之间的相互作用， 与神经元，值得重新评估至少其中的第一个 假设。 目前的数据表明，乙醇 对神经胶质细胞的影响可能实质上解释了神经元病理学 通过代谢、系统、营养或结构扰动。 我们长久以来- 长期目标是确定慢性乙醇 会造成脑损伤 因此，我们设计了两项研究， 长期乙醇对神经胶质细胞的影响 结构，海马，乙醇对神经元的影响是 有据可查 在第一项研究中，我们计划标记海马 神经元、星形胶质细胞、少突胶质细胞和具有特定细胞的小胶质细胞 分型标记物，并比较数量、大小、形状和染色强度 暴露于乙醇20周的大鼠之间的每种类型。 对照组大鼠。 一旦我们确定了各自的体内效应， 我们将采用类似的实验设计来评估 同一脑器官型组织培养模型系统的应用 地区 这种培养系统可以存活足够长的时间， 慢性乙醇研究是可能的，并保持自然组织 建筑在很大程度上。 预计乙醇将具有 对神经胶质细胞有显著的选择性作用， 模型系统将为未来的研究提供明显的优势， 与这些影响相关的机制。

Chronic alcohol abuse results in neuropsychological and brain damage, with significant medical and social costs. Much of the research into these consequences has focussed on how ethanol affects neurons, with a definite bias toward the notions that 1) ethanol is directly and specifically toxic to neurons, and 2) that neuronal pathology accounts for the neuropsychological deficits. Whether or not the former is true for physiological ethanol concentrations, an evolving appreciation of the complexity of glial cells, and their interactions with each other and with neurons, warrant reevaluating at least the first of these assumptions. Current data make a compelling argument that ethanol effects on glial cells might substantially account for neuronal pathology via metabolic, systemic, trophic, or structural perturbances. Our long- term goal is to determine the mechanisms by which chronic ethanol produces brain damage. Accordingly, we have designed two studies into the effects of long term ethanol on glial cells in a well-studied brain structure, the hippocampus, where the effects of ethanol on neurons are well documented. In the first study, we plan to label hippocampal neurons, astrocytes, oligodendrocytes, and microglia with specific cell type markers, and compare the number, size, shape and staining intensity of each type between rats exposed to ethanol for 20 wks. and nutritional control rats. Once we have established the respective in vivo effects, we will employ a similar experimental design to evaluate the potential utility of an organotypic tissue culture model system from the same brain region. This culture system is viable for sufficiently long periods that chronic ethanol studies are possible, and maintains the natural tissue architecture to a high degree. It is anticipated that ethanol will have significant and selective effects on glial cells, and that the in vitro model system will offer distinct advantages for future studies into the mechanisms associated with these effects.