Miller M W
Department of Anatomy, UMDNJ-SOM, Piscataway 08854.
Alcohol Clin Exp Res. 1988 Jun;12(3):440-9. doi: 10.1111/j.1530-0277.1988.tb00223.x.
Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation. A proliferation index, which was based on the amount of autoradiographic signal over each labeled neuron, indicated that an additional, late surge in proliferative activity occurred in Et-treated rats on GD 20-21. The amount of [3H]thymidine incorporated each day was determined by biochemical analyses. In Ct-treated rats, incorporation increased to a maximum on GD 17 and decreased thereafter. In Et-treated rats, there were two maxima, the first on GD 18 and the second on GD 20. These data fully support the findings of the autoradiographic analyses. The present data show that neuronal generation is profoundly affected by ethanol. Such disturbances result from ethanol-induced abnormalities in neuronal proliferation and migration.
产前暴露于乙醇会导致大脑皮层发育出现严重紊乱。因此，研究了子宫内乙醇暴露对神经元生成的影响。从妊娠第6天至出生当天，给怀孕大鼠喂食乙醇占总热量37.5%的液体饮食（Et组），或喂食等热量的对照饮食（Ct组）。在妊娠第10天至出生期间的某一天，给雌性大鼠注射[3H]胸腺嘧啶核苷，然后在其成熟幼崽中确定皮层神经元的起源时间。大脑采用标准放射自显影技术进行处理。乙醇暴露在神经元个体发生过程中产生了多种缺陷。Et组大鼠的神经元生成期比产前暴露于对照饮食的大鼠晚1 - 2天。此外，Et组大鼠的生成期长1 - 2天。特定日期生成的神经元数量发生了改变；从妊娠第12 - 19天，Et组大鼠生成的神经元明显少于Ct组大鼠，而在妊娠第19天之后，Et组大鼠生成的神经元更多。特定日期生成的神经元分布受到破坏；最显著的是，Et组大鼠深层皮层中晚期生成的神经元分布情况，而不是像对照组那样分布在浅层皮层。Et组大鼠的皮层神经元往往比Ct组大鼠的小，尤其是深层皮层中早期生成的神经元。尽管Et组大鼠晚期生成的神经元在深层皮层中的位置异常，但它们的大小与Ct组大鼠的相似。Ct组大鼠的神经元往往比Et组大鼠的更圆，Et组大鼠的神经元在径向方向上更具极性。基于每个标记神经元上放射自显影信号量的增殖指数表明，Et组大鼠在妊娠第20 - 21天出现了额外的晚期增殖活动高峰。每天掺入的[3H]胸腺嘧啶核苷量通过生化分析确定。在Ct组大鼠中，掺入量在妊娠第17天增加到最大值，之后下降。在Et组大鼠中，有两个最大值，第一个在妊娠第18天，第二个在妊娠第20天。这些数据充分支持了放射自显影分析的结果。目前的数据表明，神经元生成受到乙醇的深刻影响。这种干扰是由乙醇诱导的神经元增殖和迁移异常导致的。
