ETHANOL AND NERVOUS SYSTEM DEGENERATION

乙醇与神经系统退化

• 批准号: 3822999
• 负责人: H C PANT
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3822999
• 关键词: Wernicke Korsakoff syndrome; alcoholism /alcohol abuse; axon; brain metabolism; calcium metabolism; cytoskeleton; enzyme substrate; ethanol; ganglions; histopathology; ions; neural degeneration; neurochemistry; neurofilament; neurotoxins; peptidases; proteolysis; saltwater environment; toxin metabolism

Brain damage occurs in over 60% of chronic alcoholics. The causes and pathophysiology of this damage, however, are poorly understood. The general goal of our research has been to evaluate the factors that lead to alcohol-induced degeneration of the nervous system in experimental animals. Ethanol has been shown to release calcium from intracellular storage sites. The increase in cytosolic calcium activates proteases cause proteolysis of cytoskeletal proteins. The possibility exist that some of the effects of alcohol-induced degeneration may be to the activation of these proteases. In order to investigate the role of intracellular calcium during neuronal degeneration we have used the squid giant axon as a model system. The advantages of using this preparation are that the enzyme and substrates can be extruded in high yield from the giant axon, thus avoiding contamination of the preparation with nonaxonal enzymes, which may become nonspecifically attached during the homogenization of whole tissue. Second, enzyme activities and substrates present in axoplasm and axoplasmic preparations can be compared with the activities and substrates present in the region of the stellite ganglion, which contains the cell bodies of the giant axon. In the squid axon and cell body we have identified a number of immunoreactive degradation products after calcium-activated proteolysis. The results suggest that an elevation of cytosolic ionized calcium may result in a breakdown of proteins.

超过 60% 的慢性酗酒者会出现脑损伤。 其原因及 然而，人们对这种损伤的病理生理学知之甚少。 这 我们研究的总体目标是评估导致 实验中酒精引起的神经系统变性 动物。 乙醇已被证明可以从细胞内释放钙 储存地点。 细胞质钙的增加激活蛋白酶导致 细胞骨架蛋白的蛋白水解。 存在这样的可能性：其中一些 酒精引起的退化的影响可能是激活 这些蛋白酶。 为了研究细胞内钙的作用 在神经元变性期间，我们使用鱿鱼巨轴突作为模型 系统。 使用该制剂的优点是酶和 基底可以从巨轴突中以高产率挤出，从而避免 制剂被非轴突酶污染，这可能会变得 在整个组织均质化过程中非特异性附着。 二、轴浆和轴浆中存在的酶活性和底物 制剂可以与中存在的活性和底物进行比较 stellite 神经节区域，其中包含 巨大的轴突。 在鱿鱼轴突和细胞体中，我们发现了许多 钙激活蛋白水解后的免疫反应性降解产物。 结果表明，细胞质离子钙的升高可能 导致蛋白质的分解。