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可卡因对胎鼠神经元的选择性直接毒性:神经突和凋亡性神经元丢失的致畸学意义

Selective Direct Toxicity of Cocaine on Fetal Mouse Neurons: Teratogenic Implications of Neurite and Apoptotic Neuronal Loss.

作者信息

Nassogne Marie-Cécile, Evrard Philippe, Courtoy Pierre J

机构信息

Cell Biology Unit, Christian de Duve Institute of Cellular Pathology, 75, avenue Hippocrate, B-1200 Brussels, BelgiumService de Neurologie Pédiatrique, Saint Luc Hospital, University of Louvain Medical School, B-1200 Brussels, Belgium.

出版信息

Ann N Y Acad Sci. 1998 Jun;846(1):51-68. doi: 10.1111/j.1749-6632.1998.tb09726.x.

Abstract

This chapter reviews epidemiologic clinical surveys and experimental animal studies, indicating that cocaine may induce severe teratogenic effects on the developing brain. Evidence for direct toxic effects is next presented. Using cocultures of embryonic brain cells, we demonstrate that cocaine selectively affects neuronal cells, first causing a dramatic reduction in the number and length of neurites, then extensive neuronal death by apoptosis. By contrast, cocaine affected neither the abundance of astroglial cells nor their glial fibrillary acidic protein content. These effects are not due to cocaine metabolites. The contributions of indirect and direct effects that could account for cocaine neuroteratogenicity are finally discussed.

摘要

本章回顾了流行病学临床调查和实验动物研究,表明可卡因可能对发育中的大脑产生严重的致畸作用。接下来介绍直接毒性作用的证据。利用胚胎脑细胞共培养,我们证明可卡因选择性地影响神经元细胞,首先导致神经突数量和长度急剧减少,然后通过凋亡导致大量神经元死亡。相比之下,可卡因既不影响星形胶质细胞的数量,也不影响其胶质纤维酸性蛋白含量。这些作用不是由可卡因代谢物引起的。最后讨论了可能导致可卡因神经致畸性的间接和直接作用。

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