Kiper Keturah, Mild Breeann, Chen Jenny, Yuan Chongli, Wells Ellen M, Zheng Wei, Freeman Jennifer L
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Toxics. 2024 Aug 24;12(9):624. doi: 10.3390/toxics12090624.
Arsenic (As) and lead (Pb) are environmental pollutants found in common sites linked to similar adverse health effects. This study determined driving factors of neurotoxicity on the developing cerebral vasculature with As and Pb mixture exposures. Cerebral vascular toxicity was evaluated at mixture concentrations of As and Pb representing human exposures levels (10 or 100 parts per billion; ppb; µg/L) in developing zebrafish by assessing behavior, morphology, and gene expression. In the visual motor response assay, hyperactivity was observed in all three outcomes in dark phases in larvae with exposure (1-120 h post fertilization, hpf) to 10 ppb As, 10 ppb Pb, or 10 ppb mix treatment. Time spent moving exhibited hyperactivity in dark phases for 100 ppb As and 100 ppb mix treatment groups only. A decreased brain length and ratio of brain length to total length in the 10 ppb mix group was measured with no alterations in other treatment groups or other endpoints (i.e., total larval length, head length, or head width). Alternatively, measurements of cerebral vasculature in the midbrain and cerebellum uncovered decreased total vascularization at 72 hpf in all treatment groups in the mesencephalon and in all treatment groups, except the 100 ppb Pb and 10 ppb As groups, in the cerebellum. In addition, decreased sprouting and branching occurred in the mesencephalon, while only decreased branching was measured in the cerebellum. The 10 ppb Pb group showed several cerebral vasculature modifications that were aligned with a specific gene expression alteration pattern different from other treatment groups. Additionally, the 100 ppb As group drove gene alterations, along with several other endpoints, for changes observed in the 100 ppb mix treatment group. Perturbations assessed in this study displayed non-linear concentration-responses, which are important to consider in environmental health outcomes for As and Pb neurotoxicity.
砷（As）和铅（Pb）是在常见场所发现的环境污染物，它们会导致类似的不良健康影响。本研究确定了砷和铅混合暴露对发育中的脑血管系统产生神经毒性的驱动因素。通过评估行为、形态和基因表达，在代表人类暴露水平（十亿分之十或十亿分之一百；ppb；μg/L）的砷和铅混合浓度下，对发育中的斑马鱼的脑血管毒性进行了评估。在视觉运动反应试验中，在受精后1至120小时（hpf）暴露于10 ppb砷、10 ppb铅或10 ppb混合处理的幼虫的暗相中，在所有三个结果中均观察到多动。仅在100 ppb砷和100 ppb混合处理组的暗相中，移动所花费的时间表现出多动。在10 ppb混合组中测量到脑长度以及脑长度与总长度的比率降低，而其他处理组或其他终点（即幼虫总长度、头长度或头宽度）没有变化。另外，对中脑和小脑的脑血管系统测量发现，在中脑的所有处理组以及除100 ppb铅和10 ppb砷组之外的小脑的所有处理组中，在72 hpf时总血管化减少。此外，中脑出现发芽和分支减少，而小脑中仅测量到分支减少。10 ppb铅组显示出几种脑血管系统改变，这些改变与不同于其他处理组的特定基因表达改变模式一致。此外，100 ppb砷组导致了基因改变以及其他几个终点的改变，这与100 ppb混合处理组中观察到的变化一致。本研究中评估的扰动显示出非线性浓度反应，这在砷和铅神经毒性的环境卫生结果中是需要考虑的重要因素。
