Institute of Marine Research (IMR), Bergen, Norway; Nord University, Faculty of Biosciences and Aquaculture, Bodø, Norway.
Institute of Marine Research (IMR), Bergen, Norway.
Comp Biochem Physiol Part D Genomics Proteomics. 2019 Mar;29:43-54. doi: 10.1016/j.cbd.2018.11.003. Epub 2018 Nov 6.
Elevated levels of chlorpyrifos‑methyl have been detected in plant-based Atlantic salmon feeds. To evaluate the potential negative effects of long-term and continuous dietary exposure to chlorpyrifos‑methyl in fish, we fed juvenile Atlantic salmon three concentrations (0.1, 1.0 and 8.0 mg/kg) of the pesticide for about two months. Brain and liver tissues were collected after 30 and 67 days of exposure. Homogenized brain tissue was examined for effects on acetylcholinesterase, and brain and liver tissue from fish exposed to 8.0 mg/kg were used for transcriptional analysis (RNA-seq). The results showed a transient accumulation of chlorpyrifos‑methyl in the brain with lower levels after 67 days of exposure compared to after 30 days of exposure. In contrast, the liver showed a time-dependent accumulation pattern. No effect on acetylcholinesterase activity, the primary target of chlorpyrifos‑methyl, was seen in the brain. However, after 30 days of exposure, 98 significantly differentially expressed genes (DEGs) were found in brain tissue and 239 DEGs in liver tissue. After 67 days of exposure, two and 258 DEGs were found in brain and liver tissue, respectively. Continuous dietary exposure of chlorpyrifos‑methyl most profoundly affected mechanisms associated with protein degradation and lipid metabolism in both brain and liver. Specific for the brain, many of the significant DEGs encode proteins involved in neuron function. In conclusion, this study shows that chlorpyrifos‑methyl affects the transcription of genes involved in neurological function in Atlantic salmon brain, even at exposure concentrations below the threshold for systemic toxicity as seen from brain acetylcholinesterase inhibition.
植物性大西洋三文鱼饲料中已检测到甲基毒死蜱的含量升高。为了评估鱼类长期连续经口接触甲基毒死蜱的潜在负面影响，我们用三种浓度（0.1、1.0 和 8.0 mg/kg）的该农药喂养幼大西洋三文鱼约两个月。在暴露 30 和 67 天后收集大脑和肝脏组织。检查了匀浆大脑组织对乙酰胆碱酯酶的影响，以及暴露于 8.0 mg/kg 农药的鱼的大脑和肝脏组织用于转录分析（RNA-seq）。结果表明，甲基毒死蜱在大脑中的积累是短暂的，与暴露 30 天后相比，暴露 67 天后的含量较低。相比之下，肝脏表现出时间依赖性的积累模式。大脑中的乙酰胆碱酯酶活性，即甲基毒死蜱的主要靶标，没有受到影响。然而，在暴露 30 天后，大脑组织中发现了 98 个显著差异表达基因（DEGs），肝脏组织中发现了 239 个 DEGs。暴露 67 天后，大脑和肝脏组织中分别发现了 2 个和 258 个 DEGs。甲基毒死蜱的连续经口暴露对大脑和肝脏中与蛋白质降解和脂质代谢相关的机制产生了最深远的影响。具体到大脑，许多显著的 DEGs 编码与神经元功能相关的蛋白质。总之，本研究表明，甲基毒死蜱会影响大西洋三文鱼大脑中与神经功能相关的基因转录，即使在大脑乙酰胆碱酯酶抑制作用未显示出系统毒性的暴露浓度下也是如此。
