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[程序性细胞死亡的激活及中脑边缘多巴胺能系统神经元的退行性变化作为遗传性酒精成瘾的可能原因]

[Activation of programmed cell death and degenerative changes of neurons of mesocorticolimbic dopaminergic system as a possible cause of inherited alcohol addiction].

作者信息

Droblenkov A V, Karelina N R

出版信息

Morfologiia. 2012;141(1):16-22.

PMID:22724328
Abstract

It is known that the insufficiency of mesocorticolimbic dopaminergic system (MDS) lies in the basis of inherited alcohol addiction (IAA). The understanding of the pathogenesis of IAA is hampered by the absence of data on the number and volume of neuronal cell bodies in MDS and on the rate of their programmed cell death in the offspring of alcohol-dependent humans and animals. Morphological changes of neurons and macroglial cells of major MDS parts were studied in the offspring of intact Wistar rats (n = 20) and in the offspring of female rats that consumed 15% alcohol during five months, including the periods of pairing and pregnancy (n = 20). The material was obtained at 0, 5, 10, and 61 days. In brain histological sections stained with Nissl stain and using glial fibrillar acidic protein immunohistochemistry, the proportions of unaffected, hypochromic, pyknomorphic, and shadow-like neurons were determined together with the volume of unaffected neurons, oligodendrocyte, astrocyte numbers and neurono-glial index. At day 61 significant reduction in the number of unaffected and slightly changed MDS neurons was found that resulted from increased programmed cell death of neurons and their shrinkage accompanied by a partial compensatory increase in the intensity of neuron-glial interactions due to the increased number of oligodendrocytes. The alcohol addiction behavior of experimental animals was also demonstrated.

摘要

已知中脑边缘多巴胺能系统(MDS)功能不足是遗传性酒精成瘾(IAA)的基础。由于缺乏关于酒精依赖的人类和动物后代中MDS神经元细胞体数量和体积以及其程序性细胞死亡速率的数据,对IAA发病机制的理解受到阻碍。在完整的Wistar大鼠后代(n = 20)以及在五个月期间(包括配对和怀孕期)饮用15%酒精的雌性大鼠后代(n = 20)中,研究了主要MDS部位的神经元和大胶质细胞形态变化。在第0、5、10和61天获取材料。在尼氏染色和使用胶质纤维酸性蛋白免疫组织化学染色的脑组织切片中,确定未受影响、染色质减少、固缩和阴影样神经元的比例以及未受影响神经元的体积、少突胶质细胞、星形胶质细胞数量和神经胶质指数。在第61天,发现未受影响和轻微变化的MDS神经元数量显著减少,这是由于神经元程序性细胞死亡增加及其萎缩,同时由于少突胶质细胞数量增加,神经元与胶质细胞相互作用强度部分代偿性增加。还证实了实验动物的酒精成瘾行为。

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