Sodium valproate effects on the morphological and neurobehavioral phenotype of zebrafish

IF 4.2 3区 环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2024-07-06 DOI:10.1016/j.etap.2024.104500
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Abstract

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.

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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)是一种常用药物,但在发育过程中接触会产生一些负面影响。我们利用斑马鱼模型广泛分析了这些早期发育影响。斑马鱼胚胎作为卵暴露于两种亚致死浓度的 SV(10 毫克/升和 25 毫克/升)。对胚胎毒性的总体分析表明,暴露于 SV 的胚胎在心血管系统、颅面部和脊柱骨骼方面出现了广泛的异常,死亡率也很高。通过形态计量学和软骨剖面分析,证实了 SV 在蜕皮幼虫中的致畸潜力。最后,在受试者的活动、焦虑、对刺激的反应、习惯性学习和日常运动活动的同步性等方面,SV 导致的神经行为障碍都很突出,总体上反映了与自闭症谱系障碍相关的典型表型。总之,我们的研究结果证实,在发育过程中接触 SV 会产生广泛和多方面的影响。
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来源期刊
CiteScore
7.00
自引率
4.70%
发文量
185
审稿时长
34 days
期刊介绍: Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.
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