Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA; School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK.
Neurotoxicol Teratol. 2020 Mar-Apr;78:106853. doi: 10.1016/j.ntt.2019.106853. Epub 2020 Jan 3.
Farmers are often chronically exposed to insecticides, which may present health risks including increased risk of neurobehavioral impairment during adulthood and across aging. Experimental animal studies complement epidemiological studies to help determine the cause-and-effect relationship between chronic adult insecticide exposure and behavioral dysfunction. With the zebrafish model, we examined short and long-term neurobehavioral effects of exposure to either an organochlorine insecticide, dichlorodiphenyltrichloroethane (DDT) or an organophosphate insecticide chlorpyrifos (CPF). Adult fish were exposed continuously for either two or 5 weeks (10-30 nM DDT, 0.3-3 μM CPF), with short- and long-term effects assessed at 1-week post-exposure and at 14 months of age respectively. The behavioral test battery included tests of locomotor activity, tap startle, social behavior, anxiety, predator avoidance and learning. Long-term effects on neurochemical indices of cholinergic function were also assessed. Two weeks of DDT exposure had only slight effects on locomotor activity, while a longer five-week exposure led to hypoactivity and increased anxiety-like diving responses and predator avoidance at 1-week post-exposure. When tested at 14 months of age, these fish showed hypoactivity and increased startle responses. Cholinergic function was not found to be significantly altered by DDT. The two-week CPF exposure led to reductions in anxiety-like diving and increases in shoaling responses at the 1-week time point, but these effects did not persist through 14 months of age. Nevertheless, there were persistent decrements in cholinergic presynaptic activity. A five-week CPF exposure led to long-term effects including locomotor hyperactivity and impaired predator avoidance at 14 months of age, although no effects were apparent at the 1-week time point. These studies documented neurobehavioral effects of adult exposure to chronic doses of either organochlorine or organophosphate pesticides that can be characterized in zebrafish. Zebrafish provide a low-cost model that has a variety of advantages for mechanistic studies and may be used to expand our understanding of neurobehavioral toxicity in adulthood, including the potential for such toxicity to influence behavior and development during aging.
农民经常长期接触杀虫剂,这可能会带来健康风险,包括成年期和整个老年期神经行为障碍的风险增加。实验动物研究补充了流行病学研究,有助于确定慢性成年期杀虫剂暴露与行为功能障碍之间的因果关系。我们使用斑马鱼模型,研究了暴露于有机氯杀虫剂滴滴涕(DDT)或有机磷杀虫剂毒死蜱(CPF)的短期和长期神经行为影响。成年鱼连续暴露 2 或 5 周(10-30 nM DDT,0.3-3 μM CPF),分别在暴露后 1 周和 14 个月评估短期和长期影响。行为测试包括运动活动、敲击惊跳、社会行为、焦虑、捕食者回避和学习测试。还评估了长期暴露对胆碱能功能神经化学指标的影响。两周的 DDT 暴露仅对运动活动有轻微影响,而较长的五周暴露会导致暴露后 1 周时活动减少、焦虑样潜水反应增加和捕食者回避增加。当在 14 个月大时进行测试时,这些鱼表现出活动减少和惊跳反应增加。DDT 未发现明显改变胆碱能功能。两周的 CPF 暴露会导致焦虑样潜水反应减少和 1 周时聚群反应增加,但这些影响不会持续到 14 个月大。尽管如此,胆碱能前突触活性仍持续下降。五周的 CPF 暴露会导致长期影响,包括 14 个月大时的运动过度活跃和捕食者回避受损,尽管在 1 周时没有明显的影响。这些研究记录了成年期慢性接触有机氯或有机磷农药对神经行为的影响,这些影响可以在斑马鱼中得到描述。斑马鱼提供了一种低成本模型,具有多种优势,可用于机制研究,并可用于扩展我们对成年期神经行为毒性的理解,包括这种毒性对衰老过程中行为和发育的潜在影响。