Bonner A B, Marway J S, Swann M, Preedy V R
Tissue Pathology Unit, Roehampton Institute, London, UK.
Alcohol. 1996 Nov-Dec;13(6):581-7. doi: 10.1016/s0741-8329(96)00072-9.
Brain atrophy is a common feature of chronic alcohol misuse, although the pathogenic mechanisms are unknown. We propose that defects in protein synthesis are contributing events. To test this hypothesis the experimental effects of chronic (i.e., 2 and 3 weeks) ethanol feeding on brain nucleic acid composition and rates of protein synthesis in vivo were investigated. These were compared with those of skeletal muscle (represented by the plantaris). Male Wistar rats, used at mean body weights of either 82 g (first study for 2 weeks ) or 93 g (second study for 3 weeks) were fed a nutritionally complete liquid diet in which ethanol comprised a third of the total calories. Control rats were pair-fed identical amounts of the same diet, in which ethanol was substituted by isoenergetic glucose. At 2 weeks there were small reductions (i.e., approximately 5-10%) in the weight of the whole brain, cortex, and brain stem. Ethanol-induced reductions in the total protein content of the brain stem was found at 2 weeks, although these changes did not achieve significance. At 3 weeks the weights of whole brain were significantly reduced compared to a greater reduction in skeletal muscle weights. Total protein contents were reduced at 3 weeks in the whole brain and skeletal muscle. At 2 weeks there were decreases in the RNA contents of the cortex, brain stem, and entire brain. There were also reductions in cerebellum RNA composition only when expressed relative to DNA. The DNA composition of the brain was relatively unaffected by chronic ethanol feeding. At 3 weeks, total RNA and DNA were reduced in the whole brain and muscle. Fractional rates of protein synthesis (i.e., the percentage of tissue protein pool renewed each day) in the brain were unaltered after 3 weeks of ethanol feeding, but were reduced in skeletal muscles, largely as a consequence of reduced RNA composition. In conclusion, only moderate changes in the brain were found in ethanol feeding. These data can be compared to skeletal muscle, which shows that ethanol induces profound reductions in protein, RNA, and protein synthesis rates.
脑萎缩是慢性酒精滥用的常见特征，但其致病机制尚不清楚。我们认为蛋白质合成缺陷是其中的促成因素。为验证这一假设，我们研究了长期（即2周和3周）喂食乙醇对体内脑核酸组成和蛋白质合成速率的实验性影响。并将这些结果与骨骼肌（以跖肌为代表）的结果进行比较。雄性Wistar大鼠，平均体重分别为82克（为期2周的第一项研究）或93克（为期3周的第二项研究），喂食营养全面的液体饮食，其中乙醇占总热量的三分之一。对照大鼠则成对喂食相同量的相同饮食，其中乙醇被等能量的葡萄糖替代。2周时，全脑、皮质和脑干的重量有小幅减轻（即约5 - 10%）。在2周时发现乙醇导致脑干总蛋白含量降低，尽管这些变化未达到显著水平。3周时，与骨骼肌重量更大幅度的减轻相比，全脑重量显著降低。全脑和骨骼肌在3周时总蛋白含量均降低。2周时，皮质、脑干和整个大脑的RNA含量下降。仅当相对于DNA表达时，小脑RNA组成也有降低。大脑的DNA组成相对不受长期乙醇喂食的影响。3周时，全脑和肌肉中的总RNA和DNA均减少。乙醇喂食3周后，大脑中蛋白质合成的分数速率（即每天更新的组织蛋白池的百分比）未改变，但骨骼肌中的分数速率降低，这主要是由于RNA组成减少所致。总之，在喂食乙醇的情况下，大脑仅出现了适度变化。这些数据可与骨骼肌的数据进行比较，后者显示乙醇会导致蛋白质、RNA和蛋白质合成速率大幅降低。
