Abstract：
Arsenic (As) is globally detected in drinking water and food products at levels repeatedly surpassing regulatory thresholds. Several neurological and mental health risks linked to arsenic exposure are proposed; however, the nature of these effects and their association with the chemical forms of arsenic are not fully understood. Gaining a clear understanding of the etiologies and characteristics of these effects is crucial, particularly in association with developmental exposures where the nervous system is most vulnerable. In this study, we investigated the effects of early developmental exposure (6- to 120-h postfertilization [hpf]) of larval zebrafish to environmentally relevant concentrations of arsenic species-trivalent/pentavalent, inorganic/organic forms-on developmental, behavioral, and molecular endpoints to determine their effect on stress response and their potential association with stress-related disorders. At 120 hpf, the developing larvae were assessed for a battery of endpoints including survival, developmental malformities, background activity, and behavioral responses to acute visual and acoustic stimuli. Pooled larval samples were analyzed for alterations in the transcript levels of genes associated with developmental neurotoxicity and stress-related disorders. Developmental exposures at target concentrations did not significantly alter survival, overall development, or background activity, and had minor effects on developmental morphology. Sodium arsenate and monomethylarsonic acid exaggerated the behavioral responses of larval zebrafish, whereas sodium arsenite depressed them. Sodium arsenate induced significant effects on molecular biomarkers. This study highlights the effects of developmental exposure to arsenicals on the behavioral stress response, the role chemical formulation plays in exerting toxicological effects, and the possible association with stress-related disorders.
摘要：
在全球范围内，饮用水和食品中检测到的砷（As）水平反复超过监管阈值。提出了一些与砷暴露有关的神经和心理健康风险；然而，这些影响的性质及其与砷的化学形式的关联尚未完全了解。清楚了解这些影响的病因和特征至关重要，特别是与神经系统最脆弱的发育暴露有关。在这项研究中,我们调查了幼体斑马鱼的早期发育暴露（受精后6-120小时（hpf））对环境相关浓度的砷物种-三价/五价，无机/有机形式-发育，行为，和分子终点，以确定它们对应激反应的影响及其与应激相关疾病的潜在关联。在120-hpf时，对发育中的幼虫进行了一系列终点评估，包括存活，发育畸形，背景活动,以及对急性视觉和听觉刺激的行为反应。分析汇集的幼虫样品中与发育神经毒性和应激相关疾病相关的基因转录水平的改变。目标浓度的发育暴露并没有显著改变生存率，整体发展或背景活动，对发育形态影响较小。砷酸钠和单甲基肌酸夸大了斑马鱼幼虫的行为反应，亚砷酸钠抑制了他们。砷酸钠对分子生物标志物有显著影响。这项研究强调了发育暴露于砷剂对行为应激反应的影响，化学制剂在发挥毒理学作用方面的作用，以及与压力相关疾病的可能关联。
