Matsuda-Matsumoto H, Iwazaki T, Kashem M A, Harper C, Matsumoto I
Discipline of Pathology, Faculty of Medicine, The University of Sydney, NSW 2006, Australia.
Neurochem Int. 2007 Nov-Dec;51(6-7):370-6. doi: 10.1016/j.neuint.2007.04.001. Epub 2007 Apr 8.
Mild to severe cognitive impairments are frequently observed symptoms in chronic alcoholics. Decline of cognitive function significantly affects patients' recovery process and prognosis. The hippocampal region is sensitive to the effects of alcohol and it has been suggested that alcohol-induced hippocampal damage and/or changes in neuronal circuitry play an important role in generating these symptoms. Although various hypotheses have been proposed, molecular mechanisms underlying these alterations in the hippocampus are largely unknown. In the present study, we employed a 2DE-based proteomics approach to compare the protein expression profiles of the hippocampus in human alcoholic and healthy control brains. In the alcoholic hippocampus, 20 protein spots were found to be differentially regulated, 2 increased and 18 decreased. Seventeen proteins were identified using mass spectroscopy and were subcategorized into three energy metabolic proteins, six protein metabolic proteins, four signalling proteins, two oxidative stress-related proteins, one vesicle trafficking protein and one cytoskeletal protein. Some of these proteins have been previously implicated in alcohol-induced brain pathology. Based upon the results, several hypotheses were generated to explain the mechanisms underlying possible functional and/or structural alterations induced by chronic alcohol use in this brain region.
轻至重度认知障碍是慢性酒精中毒患者常见的症状。认知功能下降显著影响患者的康复进程和预后。海马区对酒精的作用敏感，有人认为酒精引起的海马损伤和/或神经回路变化在产生这些症状中起重要作用。尽管已经提出了各种假说，但海马区这些改变的分子机制在很大程度上仍不清楚。在本研究中，我们采用基于二维电泳的蛋白质组学方法，比较人类酒精中毒者和健康对照者大脑海马区的蛋白质表达谱。在酒精中毒者的海马区，发现20个蛋白质点的表达有差异，2个上调，18个下调。通过质谱鉴定出17种蛋白质，并将其分为三类：三种能量代谢蛋白、六种蛋白质代谢蛋白、四种信号蛋白、两种氧化应激相关蛋白、一种囊泡运输蛋白和一种细胞骨架蛋白。其中一些蛋白质先前已被认为与酒精引起的脑病理有关。基于这些结果，我们提出了几个假说，以解释慢性酒精使用在该脑区引起的可能的功能和/或结构改变的潜在机制。
