The anticonvulsant sodium valproate (SV) is frequently administered as a medicament but bears several negative effects in case of exposure during development. We analyzed extensively these early development effects of using the zebrafish model. Zebrafish embryos were exposed as eggs to two sublethal concentrations of SV, 10 and 25 mg/L. A general embryo toxicity analysis revealed extended anomalies in the cardiovascular system, and in the craniofacial and the spinal skeleton, as well as high mortality, in the embryos exposed to SV. The teratogenic potential of SV was confirmed in hacthed larvae by morphometric and cartilage profile analysis. Last, neurobehavioral impairments due to SV were highlighted in subjects’ activity, anxiety, response to stimulations, habituation learning, and daily synchronization of locomotor activity, overall mirroring typical phenotypes associated with autistic spectrum disorders. In conclusion, our results confirmed the presence of extended and multifaced impacts of exposure to SV during development.

中文翻译：

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丙戊酸钠对斑马鱼形态和神经行为表型的影响


抗惊厥药丙戊酸钠 (SV) 经常作为药物使用，但在开发过程中暴露时会产生一些负面影响。我们广泛分析了使用斑马鱼模型的这些早期发育效应。斑马鱼胚胎作为卵暴露于两种亚致死浓度的 SV，10 和 25 mg/L。一般胚胎毒性分析显示，接触 SV 的胚胎存在心血管系统、颅面和脊柱骨骼的广泛异常，以及高死亡率。通过形态测定和软骨轮廓分析证实了 SV 在孵化幼虫中的致畸潜力。最后，由 SV 引起的神经行为损伤在受试者的活动、焦虑、刺激反应、习惯化学习和日常运动活动同步方面突出，总体上反映了与自闭症谱系障碍相关的典型表型。总之，我们的结果证实了在发育过程中暴露于 SV 会产生广泛和多方面的影响。