Pierce D R, Goodlett C R, West J R
Department of Anatomy, College of Medicine, University of Iowa, Iowa City 52242.
Teratology. 1989 Aug;40(2):113-26. doi: 10.1002/tera.1420400205.
Neonatal rats were exposed to 6.6 g/kg of alcohol each day between postnatal days 4 and 10 while artificial-rearing procedures were used, in a manner which produced high peak and low trough blood alcohol concentrations each day. Gastrostomy controls were reared artificially with maltose/dextrin isocalorically substituted for alcohol in the milk formula, and suckle controls were reared normally by dams. The pups were sacrificed on day 10 and tissue sections (2 microns thick) were obtained in the sagittal plane through the cerebellum and in the horizontal plane through the hippocampal formation. Overall area measures were obtained for the hippocampus proper, area dentata, and cerebellum, along with areas of the cell layers of these regions. In the hippocampal formation, cell counts were made of the pyramidal cells of the hippocampus proper, the multiple cell types of the hilus, and the granule cells of the area dentata. In the cerebellum, cell counts of Purkinje cells, granule cells of the granular layer, granule cells of the external granular layer, and mitotic cells of the external granular layer were obtained from lobules I, V, VII, VIII, and IX. Alcohol selectively reduced areas and neuronal numbers in the cerebellum but had no significant effects on neuronal numbers in the hippocampal formation. Purkinje cells exhibited the greatest percent reductions, and cerebellar granule cells were significantly reduced in the granular layer but not in the external granular layer. All lobules showed these effects, but lobule I was significantly more affected than the other four lobules that were analyzed. The results demonstrate the differential vulnerability of selected neuronal populations to the developmental toxicity of alcohol exposure during the brain growth spurt.
在出生后第4天至第10天期间，采用人工饲养方法，每天给新生大鼠喂食6.6克/千克酒精，使大鼠每天的血酒精浓度出现高峰和低谷。胃造口对照组用麦芽糖/糊精等热量替代牛奶配方中的酒精进行人工饲养，哺乳对照组由母鼠正常哺乳。在第10天将幼鼠处死，获取矢状面穿过小脑和水平面穿过海马结构的组织切片（2微米厚）。测量海马体、齿状回和小脑的总面积，以及这些区域细胞层的面积。在海马结构中，对海马体的锥体细胞、海马沟的多种细胞类型以及齿状回的颗粒细胞进行细胞计数。在小脑中，从小脑的I、V、VII、VIII和IX小叶获取浦肯野细胞、颗粒层颗粒细胞、外颗粒层颗粒细胞以及外颗粒层有丝分裂细胞的细胞计数。酒精选择性地减少了小脑的面积和神经元数量，但对海马结构中的神经元数量没有显著影响。浦肯野细胞减少的百分比最大，颗粒层的小脑颗粒细胞显著减少，但外颗粒层没有减少。所有小叶都有这些影响，但I小叶比其他四个被分析的小叶受影响更显著。结果表明，在脑发育快速期，特定神经元群体对酒精暴露的发育毒性具有不同的易感性。
