Putzke J, De Beun R, Schreiber R, De Vry J, Tölle T R, Zieglgänsberger W, Spanagel R
Max-Planck-Institute of Psychiatry, Munich, Germany.
Brain Res Mol Brain Res. 1998 Nov 20;62(2):196-205. doi: 10.1016/s0169-328x(98)00253-8.
Chronic alcohol intoxication is known to produce neuronal degeneration in the central and peripheral nervous system of experimental animals and of humans. It is suggested that various components of the cytoskeleton undergo profound changes following chronic alcohol use and misuse. Here we studied the expression of the neuronal cytoskeletal microtubule-associated protein 2 (MAP2) following long-term alcohol consumption and subsequent alcohol withdrawal. Alcohol-preferring AA (Alko Alkohol) rats with a high voluntary alcohol consumption for a period of 16 months were compared with age-matched control rats without prior experience with alcohol. For comparison, in a second experiment, heterogeneous Wistar rats that also had voluntary access to alcohol for 8 months were examined following alcohol consumption and withdrawal. In situ hybridization and subsequent dot blot and Northern blot analysis for further quantification revealed that chronically alcoholized animals exhibit markedly decreased MAP2 mRNA levels in several parts of the extrapyramidal system (mainly in the caudate putamen, the substantia nigra pars compacta and the globus pallidus), the mesolimbic system, in several hypothalamic nuclei and in the nucleus inferior colliculus. Other areas such as the hippocampus, frontoparietal cortex and cerebellum were less affected by chronic alcohol intake, however, in these regions the MAP2 mRNA levels were increased during alcohol withdrawal. These results suggest that long-term alcohol self-administration affects central neurons involved in motor control via the influence on the integrity of the cytoskeleton and may thus induce motor dysfunction.
已知慢性酒精中毒会在实验动物和人类的中枢及外周神经系统中导致神经元变性。有人提出，长期饮酒和酗酒会使细胞骨架的各种成分发生深刻变化。在此，我们研究了长期饮酒及随后戒酒过程中神经元细胞骨架微管相关蛋白2（MAP2）的表达情况。将自愿大量饮酒16个月的嗜酒AA（阿尔科酒精）大鼠与年龄匹配、无饮酒经历的对照大鼠进行比较。为作比较，在第二个实验中，对同样自愿饮酒8个月的杂种Wistar大鼠在饮酒及戒酒后进行了检查。原位杂交以及随后用于进一步定量分析的斑点印迹和Northern印迹分析表明，长期饮酒的动物在锥体外系的几个部位（主要是尾状壳核、黑质致密部和苍白球）、中脑边缘系统、几个下丘脑核以及下丘脑中，MAP2 mRNA水平显著降低。而海马体、额顶叶皮质和小脑等其他区域受慢性酒精摄入的影响较小，不过在这些区域，MAP2 mRNA水平在戒酒期间有所升高。这些结果表明，长期自我饮酒通过影响细胞骨架的完整性，对参与运动控制的中枢神经元产生影响，进而可能导致运动功能障碍。
