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Neurobehavioral effects of 1,2-propanediol in zebrafish (Danio rerio).
NeuroToxicology ( IF 3.4 ) Pub Date : 2018-02-09 , DOI: 10.1016/j.neuro.2018.02.007
Andrey Massarsky 1 , Ayham Abdel 1 , Lilah Glazer 2 , Edward D Levin 2 , Richard T Di Giulio 1
Affiliation  

The use of electronic cigarettes (e-cigarettes) is increasing despite insufficient information concerning their long-term effects, including the effects of maternal e-cigarette use on pre- and postnatal development. Our previous study demonstrated that developmental exposure to 1,2-propanediol (a principal component of e-cigarette liquid) affected early development of zebrafish, causing reduced growth, deformities, and hyperactive swimming behavior in larvae. The current study extends assessment of the developmental toxicity of 1,2-propanediol by examining additional long-term behavioral effects. We demonstrate that embryonic/larval exposure of zebrafish to 1,2-propanediol (0.625% or 1.25%) not only affected behavioral parameters in the larvae, but also caused persisting behavioral effects in adults after early developmental exposure. Additional parameters, including neural and vascular development in larvae, stress response in adults, and concentration of neurotransmitters dopamine and serotonin in adult brain were examined, in order to explain the behavioral differences. These additional assessments did not find 1,2-propanediol exposure to significantly affect Tg(Neurog1:GFP) or the transcript abundance of neural genes (Neurog1, Ascl1a, Elavl3, and Lef1). Vascular development was not found to be affected by 1,2-propanediol exposure, as inferred from experiments with Tg(Flk1:eGFP) zebrafish; however, transcript abundance of vascular genes (Flk1, Vegf, Tie-2, and Angpt1) was decreased. No statistically significant changes were noted for plasma cortisol or brain neurotransmitters in adult fish. Lastly, analysis of gene transcripts involved with 1,2-propanediol metabolism (Adh5, Aldh2.1, and Ldha) showed an increase in Adh5 transcript. This is the first study to demonstrate that developmental exposure to 1,2-propanediol has long-term neurobehavioral consequences in adult zebrafish, showing that e-cigarettes contain substances potentially harmful to neurodevelopment.

中文翻译:

1,2-丙二醇在斑马鱼(Danio rerio)中的神经行为作用。

尽管没有足够的关于电子烟(包括产妇使用电子烟对产前和产后发育的影响)的长期影响的信息,但电子烟(电子烟)的使用仍在增加。我们以前的研究表明,发育暴露于1,2-丙二醇(电子烟液体的主要成分)会影响斑马鱼的早期发育,从而导致幼虫的生长,畸形和过度活跃的游泳行为减少。当前的研究通过检查其他长期行为影响,扩展了对1,2-丙二醇发育毒性的评估。我们证明斑马鱼的胚胎/幼虫暴露于1,2-丙二醇(0.625%或1.25%)不仅影响幼虫的行为参数,而且在早期发育暴露后还会对成年人造成持续的行为影响。为了解释行为差异,还检查了其他参数,包括幼虫的神经和血管发育,成人的应激反应以及成人大脑中神经递质多巴胺和5-羟色胺的浓度。这些额外的评估未发现1,2-丙二醇的暴露会显着影响Tg(Neurog1:GFP)或神经基因(Neurog1,Asc1a,Elavl3和Lef1)的转录本丰度。从Tg(Flk1:eGFP)斑马鱼的实验推断,未发现血管发育受到1,2-丙二醇暴露的影响。但是,血管基因(Flk1,Vegf,Tie-2和Angpt1)的转录本丰度降低了。在成年鱼中,血浆皮质醇或脑神经递质没有发现统计学上的显着变化。最后,分析与1,2-丙二醇代谢有关的基因转录本(Adh5,Aldh2.1和Ldha)显示Adh5转录本增加。这是第一项证明发育暴露于1,2-丙二醇对成年斑马鱼具有长期神经行为影响的研究,表明电子烟中含有对神经发育潜在有害的物质。
更新日期:2018-02-09
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