Nonhuman primate model of the effect of prenatal cocaine exposure on cerebral cortical development
Nonhuman primate model of the effect of prenatal cocaine exposure on cerebral cortical development
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DOI：
10.1111/j.1749-6632.1998.tb09736.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Lidow, MS
中科院分区：
文献类型：
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作者：
Lidow, MS
为了研究产前可卡因暴露对灵长类动物皮质生成的影响，我们建立了一个猴模型，在该模型中，妊娠动物从妊娠第40天至第102天每天两次口服10 mg/kg可卡因。这些动物在足月分娩，并检查了2个月和1.5岁婴儿的大脑。检查发现整个大脑卡特的结构异常，这是预期的非选择性扩散循环衍生的单胺的调制。它们包括：（1）皮质细胞数量减少，这很可能反映了异常的细胞增殖;（2）皮质神经元的不适当定位，这是由皮质细胞迁移的改变引起的;和（3）胶质形态改变。结构改变伴随着动物气质的异常，让人想起那些在滥用药物的母亲的人类婴儿中看到的。正如形态学研究所预测的那样，我们发现可卡因治疗对胎儿大脑壁的额叶、顶叶、颞叶和枕叶区域的所有层的单胺及其受体水平产生了显着的变化。这表明，孕妇滥用可卡因可能会影响胎儿大脑中单胺的总体水平，并在这样做的过程中，干扰这些化学物质调节的广泛的发育事件。
To investigate the effects of prenatal cocaine exposure on the corticogenesis in primates we developed a monkey model in which pregnant animals received 10 mg/kg cocaine orally twice a day from the 40th to the 102nd day of pregnancy. The animals gave birth at term, and brains of the 2-month and 1.5-year-old infants were examined. Examination revealed the structural abnormalities throughout the cerebral carter that would be expected from modulation of the nonselectively diffusing circulation-derived monoamines. They include: (1) reduction in the number of cortical cells, which most likely reflects abnormal cell proliferation; (2) inappropriate positioning of cortical neurons, which resulted from alterations in migration of cortical cells; and (3) altered glial morphology. The structural alterations were accompanied by abnormalities in animal temperament reminiscent of those seen in human infants of drug-abusing mothers. As predicted by the morphologic studies, we found that cocaine treatment produced significant changes in the levels of monoamines and their receptors in all laminae of the frontal, parietal, temporal, and occipital regions of the fetal cerebral wail. This indicates that cocaine abuse by pregnant human mothers may affect the global levels of monoamines in the fetal brain and, in doing so, interfere with a broad range of developmental events regulated by these chemicals.