CHRONIC ETHANOL EFFECTS ON BRAIN GLIAL CELLS

长期酗酒会导致神经心理和大脑损伤， 带来巨大的医疗和社会成本。许多关于 这些后果主要集中在乙醇如何影响神经元， 对1)乙醇是直接和直接的 特别是对神经元的毒性，以及2)神经元病理 治疗神经心理缺陷。不管前者是不是真的 对于生理乙醇浓度，对 神经胶质细胞的复杂性，以及它们之间的相互作用和 对于神经元，至少需要重新评估其中的第一个 假设。目前的数据提出了一个令人信服的论点，乙醇 对神经胶质细胞的影响可能是神经元病理的重要原因 通过新陈代谢、全身、营养或结构上的扰动。我们的长- 学期目标是确定慢性酒精 会造成大脑损伤。因此，我们设计了两项研究，以 长期酒精对脑内神经胶质细胞的影响 结构，海马体，乙醇对神经元的影响是 有据可查。在第一项研究中，我们计划将海马体 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 键入标记，并比较标记的数量、大小、形状和染色强度 每种类型的大鼠暴露于乙醇20周之间。和营养价值 控制老鼠。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这种潜力 同脑器官型组织培养模型系统的应用 区域。这种培养系统在足够长的时间内是可行的 慢性乙醇研究是可能的，并保持了自然组织 高度的建筑。预计乙醇将具有 对胶质细胞的显著和选择性作用，以及在体外 模型系统将为未来的研究提供明显的优势 与这些效应相关的机制。

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.