评估环境化学品的发育神经毒性:研究机制和确定潜在的生物标志物

Dr. Ambreen Siddique
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摘要

背景:暴露于环境化学品所导致的发育神经毒性是一个重大的公共健康问题。了解这种神经毒性的内在机制并确定潜在的生物标志物对于早期检测和有效的风险评估至关重要。研究目的本研究旨在评估特定环境化学品的发育神经毒性,并调查其潜在机制。此外,该研究还试图确定潜在的生物标志物,以便及早发现和监测发育神经毒性。研究方法建立体外神经发育模型,包括神经元细胞培养和类器官系统,以评估环境化学物质的神经毒性效应。采用适当的检测方法和成像技术对神经元活力、形态、神经元突起生长、突触发生和突触活动等关键终点进行评估。机理研究包括通过基因表达分析、蛋白质分析和信号通路研究,探索氧化应激、炎症、神经递质系统破坏和神经发育过程干扰。研究结果体外模型暴露于选定的环境化学物质会导致明显的神经毒性效应,包括神经元活力受损、形态发育紊乱和突触活动改变。机理研究表明,氧化应激和神经递质系统紊乱参与了所观察到的神经毒性。此外,一些潜在的生物标志物,包括基因表达变化和表观遗传修饰,与发育期神经毒性有显著的相关性。结论本研究在体外神经发育模型中证明了环境化学物质的发育神经毒性。研究结果凸显了氧化应激和神经递质干扰是神经毒性效应的关键机制。此外,潜在生物标志物的鉴定为早期检测和监测发育期神经毒性提供了很好的途径。这些结果有助于人们更好地理解神经发育过程中接触环境化学物质所带来的风险,并对风险评估和监管指南产生影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Assessment of the Developmental Neurotoxicity of Environmental Chemicals: Investigating the Mechanisms & Identifying Potential Biomarkers
Background: Developmental neurotoxicity resulting from exposure to environmental chemicals is a significant public health concern. Understanding the mechanisms underlying such neurotoxicity and identifying potential biomarkers are essential for early detection and effective risk assessment. Objective: This study aimed to assess the developmental neurotoxicity of selected environmental chemicals and investigate the underlying mechanisms. Additionally, the study sought to identify potential biomarkers for early detection and monitoring of developmental neurotoxicity. Methods: In vitro neurodevelopmental models were established, including neuronal cell cultures and organoid systems, to evaluate the neurotoxic effects of environmental chemicals. Key endpoints, such as neuronal viability, morphology, neurite outgrowth, synaptogenesis, and synaptic activity, were assessed using appropriate assays and imaging techniques. Mechanistic investigations involved exploring oxidative stress, inflammation, disruption of neurotransmitter systems, and interference with neurodevelopmental processes through gene expression analysis, protein profiling, and signaling pathway investigations. Results: Exposure of the in vitro models to selected environmental chemicals resulted in significant neurotoxic effects, including impaired neuronal viability, disrupted morphological development, and altered synaptic activity. Mechanistic investigations revealed the involvement of oxidative stress and disruption of neurotransmitter systems in the observed neurotoxicity. Furthermore, several potential biomarkers, including gene expression changes and epigenetic modifications, showed significant correlations with developmental neurotoxicity. Conclusion: This study demonstrates the developmental neurotoxicity of environmental chemicals in in vitro neurodevelopmental models. The findings highlight the role of oxidative stress and neurotransmitter disruption as key mechanisms underlying neurotoxic effects. Moreover, the identification of potential biomarkers provides promising avenues for early detection and monitoring of developmental neurotoxicity. These results contribute to a better understanding of the risks associated with environmental chemical exposure during neurodevelopment and have implications for risk assessment and regulatory guidelines.
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