Miller M W
Research Service, Veterans Affairs Medical Center, Iowa City, Iowa.
Alcohol Clin Exp Res. 1993 Apr;17(2):304-14. doi: 10.1111/j.1530-0277.1993.tb00768.x.
Rats prenatally exposed to ethanol exhibit a variety of structural anomalies in the central nervous system. One of the key features of experimental fetal alcohol syndrome is microencephaly. Cerebral cortex is particularly susceptible to the effects of prenatal exposure to ethanol. Its total mass is reduced, it is thinner, and it contains fewer neurons and glia. Various studies in rats and humans suggest that chronic early exposure to ethanol leads to a massive reorganization of cortex characterized by heterotopic clusters of neurons. A pulse and chase study with [3H]thymidine autoradiography was used to determine if gestational exposure to ethanol leads to defects in neuronal migration. Rats were fed an ethanol-containing diet between gestational day (G) 6 and G21, pair-fed a liquid control diet, or fed chow. Ethanol delayed the migration of early-generated neurons (those born on G13) to deep cortex by 2 days. Moreover, the migration of late-generated neurons (those born on G21) was delayed 4 to 6 days by ethanol, and often these neurons terminated their migration in ectopic locations. Ethanol significantly decreased the rate of migration and the time postmitotic cells remained in the proliferative zones. On the other hand, ethanol did not have a significant effect on the rate of cortical expansion and the fraction of cells that left the proliferating population in order to migrate to cortex. Thus, the migration of young neurons was profoundly altered by prenatal exposure to ethanol. Such delays may lead to a desynchronization of cortical development that makes it impossible for cortical neurons to establish a normal circuitry.
产前暴露于乙醇的大鼠在中枢神经系统中表现出多种结构异常。实验性胎儿酒精综合征的关键特征之一是小头畸形。大脑皮层对产前暴露于乙醇的影响特别敏感。其总质量减少，变薄，且神经元和神经胶质细胞数量减少。对大鼠和人类的各种研究表明，早期长期暴露于乙醇会导致皮层大规模重组，其特征是神经元异位聚集。使用[3H]胸腺嘧啶放射自显影的脉冲追踪研究来确定孕期暴露于乙醇是否会导致神经元迁移缺陷。在妊娠第6天（G）至G21天期间，给大鼠喂食含乙醇的饮食，对其进行配对喂食液体对照饮食，或喂食普通食物。乙醇使早期生成的神经元（那些在G13天出生的）向深层皮层的迁移延迟了2天。此外，乙醇使晚期生成的神经元（那些在G21天出生的）的迁移延迟了4至6天，并且这些神经元常常在异位位置终止迁移。乙醇显著降低了迁移速率以及有丝分裂后细胞停留在增殖区的时间。另一方面，乙醇对皮层扩张速率以及离开增殖群体以迁移至皮层的细胞比例没有显著影响。因此，产前暴露于乙醇会深刻改变年轻神经元的迁移。这种延迟可能导致皮层发育不同步，使得皮层神经元无法建立正常的神经回路。
