Valproic acid induced abnormal development of the central nervous system of three species of amphibians: implications for neural tube defects and alternative experimental systems.
Valproic acid induced abnormal development of the central nervous system of three species of amphibians: implications for neural tube defects and alternative experimental systems.
复制标题
丙戊酸诱导三种两栖动物中枢神经系统的异常发育：对神经管缺陷和替代实验系统的影响。
DOI：
10.1002/tcm.1770120603
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
F. Kirschbaum
中科院分区：
文献类型：
--
作者：
A. Oberemm;F. Kirschbaum
从囊胚期（S）9至对照胚胎的晚期原肠胚形成（S 11 1/2-12），将墨西哥钝口线虫、非洲爪蟾和黄绿Hyperolius viridiflavus taeniatus的胚胎暴露于不同浓度的丙戊酸（VPA：0.1、1.5、10 mM）。在10和5 mM VPA下，所有供试种属的早期发育均受到影响。然而，最明显的影响发生在钝口鱼：神经褶皱出现延迟，并表现出扁平和波浪形;神经管没有形成，胚胎相继死亡。在非洲爪蟾和Hyperolius（10，5毫米VPA）的原肠胚形成的开始被推迟到神经元形成的控制胚胎。在非洲爪蟾的许多胚胎完成神经形成，而一些胚胎暴露于10 mM VPA显示不同类型和程度的神经管缺陷（NTDs）（开放神经管在不同地区的背部）。在Hyperolius中，胚孔周围出现神经褶皱，随后融合（在5 mM VPA处理的胚胎中更早），但这些胚胎的形状异常，发育不继续（10 mM VPA时效果显著）。比较这三个物种，爪蟾被证明是最不敏感的物种（在5 mM VPA 14.2%NTD的总畸形相比，100%的其他物种）。最敏感的物种，Ambystoma，在1 mM VPA时出现头部水肿，而无尾两栖动物则不受影响。我们的研究结果表明，VPA诱导的NTDs在哺乳动物和两栖动物中的机制相似。
Embryos of Ambystoma mexicanum, Xenopus laevis, and Hyperolius viridiflavus taeniatus were exposed to various concentrations of valproic acid (VPA: 0.1, 1.5, 10 mM) from blastula stage (S) 9 on up to advanced gastrulation of control embryos (S 11 1/2-12). At 10 and 5 mM VPA early development was affected in all species tested. However, the most pronounced effects occurred in Ambystoma: the neural folds appeared delayed and showed a flattened and wavy shape; the neural tube was not formed and embryos successively died. In Xenopus and Hyperolius (10, 5 mM VPA) the beginning of gastrulation was delayed up to neurulation of control embryos. In Xenopus many of the embryos completed neurulation, whereas some embryos exposed to 10 mM VPA showed neural tube defects (NTDs) of different type and degree (open neural tube at different regions of the dorsum). In Hyperolius neural folds arose around the blastoporus and fused later on (earlier in embryos treated with 5 mM VPA), but the shape of these embryos was abnormal and the development was not continued (pronounced effect at 10 mM VPA). Comparing the three species, Xenopus proved to be the least sensitive species (at 5 mM VPA 14.2% NTDs of total malformations compared to 100% in the other species). The most sensitive species, Ambystoma, developed head-oedema at 1 mM VPA, whereas the anurans were not affected. Our results suggest a similar mechanism of VPA-induced NTDs in mammals and amphibians.