MIGRATION OF CORTICAL-NEURONS IS ALTERED BY GESTATIONAL EXPOSURE TO ETHANOL

MIGRATION OF CORTICAL-NEURONS IS ALTERED BY GESTATIONAL EXPOSURE TO ETHANOL
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DOI:
10.1111/j.1530-0277.1993.tb00768.x
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发表时间:
1993-04-01
影响因子:
3.2
通讯作者:
MILLER, MW
MILLER, MW
中科院分区:
医学3区
文献类型:
--
作者:
MILLER, MW

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产前接触乙醇的大鼠中枢神经系统表现出多种结构异常。实验性胎儿酒精综合症的主要特征之一是小脑畸形。大脑皮层特别容易受到产前接触乙醇的影响。它的总质量减少了。它更薄,并且包含更少的神经元和神经胶质细胞。对大鼠和人类的各种研究表明,长期早期接触乙醇会导致以异位神经元簇为特征的皮层大规模重组。使用[H-3]胸苷放射自显影进行脉冲和追踪研究来确定妊娠期接触乙醇是否会导致神经元迁移缺陷。在妊娠第 6 天和第 21 天之间,给大鼠喂食含乙醇的饮食,配对喂食液体对照饮食,或喂食食物。乙醇使早期生成的神经元(那些在 G13 出生的神经元)向深层皮层的迁移延迟了 2 天。此外,晚生神经元(G21 出生的神经元)的迁移被乙醇延迟了 4 至 6 天,并且这些神经元通常在异位位置终止其迁移。乙醇显着降低了迁移率和有丝分裂后细胞在增殖区的停留时间。另一方面,乙醇对皮质扩张速率和离开增殖群体以迁移到皮质的细胞分数没有显着影响。因此,年轻神经元的迁移因产前接触乙醇而发生了深刻的改变。这种延迟可能会导致皮质发育不同步,从而使皮质神经元无法建立正常的电路。
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 [H-3]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.