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丙戊酸和4-烯丙戊酸的体外神经致畸性。

In vitro neuroteratogenicity of valproic acid and 4-en-VPA.

作者信息

Gofflot F, Nassogne M C, Etzion T, Van Maele-Fabry G, Evrard P, Picard J J

机构信息

Laboratory of Developmental Genetics, Catholic University of Louvain, Louvain-La-Neuve, Belgium.

出版信息

Neurotoxicol Teratol. 1995 Jul-Aug;17(4):425-35. doi: 10.1016/0892-0362(94)00094-t.

DOI:10.1016/0892-0362(94)00094-t
PMID:7565489
Abstract

Mouse embryos displaying 8 to 9 pairs of somites were cultured during 26 h in presence of 0.75 mM of VPA, or of 1 mM of 4-en-VPA. These concentrations induced approximately 50% of dysmorphogenic embryos. Irregular suture of caudal neural tube, abnormal head shape, cranial neural tube defects, and deformed optic vesicles were the most common defects observed with both compounds. The main differences in the types of dysmorphogeneses detected between the two compounds concerned the suture of the caudal neural tube and the telencephalic region. Other macroscopic effects induced by the two compounds were similar. Several of the observed abnormalities can be correlated with defects reported after in vivo exposure. The major alteration of the histological structure of the neural tube concerned a specific area in the hindbrain : VPA and 4-en-VPA induced an abnormal and irregular budding of the neuroepithelium at this level. Immunohistology with an antibody specific for radial glial fibers (RC-2) as well as SEM analysis showed a moderate effect on glial development, mainly after exposure to VPA.

摘要

具有8至9对体节的小鼠胚胎在含有0.75 mM丙戊酸(VPA)或1 mM 4-烯丙戊酸(4-en-VPA)的条件下培养26小时。这些浓度诱导了约50%的畸形胚胎。尾神经管不规则缝合、头部形状异常、颅神经管缺陷和视泡变形是两种化合物观察到的最常见缺陷。两种化合物检测到的畸形类型的主要差异涉及尾神经管和端脑区域的缝合。两种化合物诱导的其他宏观效应相似。观察到的一些异常与体内暴露后报告的缺陷相关。神经管组织结构的主要改变涉及后脑的一个特定区域:VPA和4-en-VPA在该水平诱导神经上皮异常且不规则的出芽。用针对放射状胶质纤维的特异性抗体(RC-2)进行免疫组织学以及扫描电镜分析显示,主要在暴露于VPA后,对胶质细胞发育有中度影响。

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