Crandall James E, Hackett Hazel E, Tobet Stuart A, Kosofsky Barry E, Bhide Pradeep G
E.K. Shriver Center for Mental Retardation, University of Massachusetts Medical School, Waltham, MA 02452, USA.
Cereb Cortex. 2004 Jun;14(6):665-75. doi: 10.1093/cercor/bhh027. Epub 2004 Mar 28.
Recurrent exposure of the developing fetus to cocaine produces persistent alterations in structure and function of the cerebral cortex. Neurons of the cerebral cortex are derived from two sources: projection neurons from the neuroepithelium of the dorsal pallium and interneurons from the ganglionic eminence of the basal telencephalon. The interneurons are GABAergic and reach the cerebral cortex via a tangential migratory pathway. We found that recurrent, transplacental exposure of mouse embryos to cocaine from embryonic day 8 to 15 decreases tangential neuronal migration and results in deficits in GABAergic neuronal populations in the embryonic cerebral wall. GABAergic neurons of the olfactory bulb, which are derived from the ganglionic eminence via the rostral migratory pathway, are not affected by the cocaine exposure suggesting a degree of specificity in the effects of cocaine on neuronal migration. Thus, one mechanism by which prenatal cocaine exposure exerts deleterious effects on cerebral cortical development may be by decreasing GABAergic neuronal migration from the ganglionic eminence to the cerebral wall. The decreased GABA neuron migration may contribute to persistent structural and functional deficits observed in the exposed offspring.
发育中的胎儿反复接触可卡因会导致大脑皮质的结构和功能发生持续性改变。大脑皮质的神经元有两个来源：背侧 pallium 的神经上皮的投射神经元和基底前脑的神经节隆起的中间神经元。中间神经元是γ-氨基丁酸能的，并通过切向迁移途径到达大脑皮质。我们发现，从胚胎第8天到15天，将小鼠胚胎反复经胎盘暴露于可卡因会减少切向神经元迁移，并导致胚胎脑壁中γ-氨基丁酸能神经元群体出现缺陷。嗅球的γ-氨基丁酸能神经元通过吻侧迁移途径从神经节隆起衍生而来，不受可卡因暴露的影响，这表明可卡因对神经元迁移的影响具有一定程度的特异性。因此，产前接触可卡因对大脑皮质发育产生有害影响的一种机制可能是减少γ-氨基丁酸能神经元从神经节隆起向脑壁的迁移。γ-氨基丁酸能神经元迁移减少可能导致在暴露后代中观察到的持续性结构和功能缺陷。
