Perinatal Exposure to the Neonicotinoid Thiacloprid Impacts Transcription of Neuroplasticity and Neuroendocrine Markers in Mice but Not in the Zebrafish Model.

IF 2.8 4区 医学 Q3 TOXICOLOGY
Kirthana Kunikullaya U, Zuzanna M Baran, Pascal Coumailleau, Laetitia Guillot, Harry W M Steinbusch, Fatima Smagulova, Thierry D Charlier
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Abstract

Neonicotinoids are widely used insecticides in agriculture, aquaculture, pet care, and urban pest control. Initially developed to selectively target the insect cholinergic system, their extensive use has raised concerns about adverse effects on nontarget vertebrates. This study investigated the developmental neurotoxicity of the neonicotinoid thiacloprid using two vertebrate models: zebrafish and mice. Transgenic cyp19a1b-GFP zebrafish eleutheroembryos, which report estrogenic activity, were exposed to thiacloprid (10-6-10-8 M) for 4-5 days. No significant changes were observed in GFP expression or neuroplasticity and neuroendocrine markers, suggesting a limited impact in this aquatic model. In contrast, prenatal exposure of mice to thiacloprid (0.06, 0.6, or 6 mg/kg/day from embryonic day 6.5 to 15.5) produced dose-, sex-, and region-specific alterations in brain gene expression during adolescence (postnatal day 35). At low to mid doses, markers of neurogenesis and plasticity, such as doublecortin in the amygdala, neurogenin, nestin, and PCNA in the hippocampus and cerebellum, were upregulated. However, high-dose exposure (6 mg/kg/day) led to reduced expression of these markers, including BDNF in the hypothalamus and PCNA in the hippocampus, particularly in females. These results indicate that thiacloprid, even at low doses, can subtly but significantly affect mammalian brain development. Further research is needed to assess the neurodevelopmental risks of neonicotinoids in vertebrates, including humans.

围产期暴露于新烟碱类噻虫啉对小鼠神经可塑性和神经内分泌标志物转录的影响,但对斑马鱼模型没有影响。
新烟碱类杀虫剂广泛应用于农业、水产养殖、宠物护理和城市害虫防治等领域。最初是为了选择性地靶向昆虫胆碱能系统而开发的,它们的广泛使用引起了对非靶向脊椎动物的不利影响的担忧。本研究采用斑马鱼和小鼠两种脊椎动物模型研究了新烟碱类噻虫啉的发育神经毒性。将具有雌激素活性的转基因cyp19a1b-GFP斑马鱼幼鱼胚胎暴露于噻虫啉(10-6-10-8 M)中4-5天。未观察到GFP表达、神经可塑性和神经内分泌标志物的显著变化,表明对该水生模型的影响有限。相比之下,小鼠产前暴露于噻虫啉(0.06、0.6或6mg /kg/天,从胚胎期第6.5天至15.5天)会在青春期(出生后第35天)产生剂量、性别和区域特异性的脑基因表达改变。在低至中剂量下,杏仁核中的双皮质素、海马和小脑中的神经原素、巢素和PCNA等神经发生和可塑性标志物上调。然而,高剂量暴露(6mg /kg/天)导致这些标记物的表达减少,包括下丘脑中的BDNF和海马中的PCNA,特别是在女性中。这些结果表明,即使是低剂量的噻虫啉,也能微妙但显著地影响哺乳动物的大脑发育。需要进一步的研究来评估新烟碱类对脊椎动物(包括人类)的神经发育风险。
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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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