National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
Sci Total Environ. 2021 Mar 1;758:143694. doi: 10.1016/j.scitotenv.2020.143694. Epub 2020 Nov 24.
The organophosphate flame retardant, tris (1-chloro-2-propyl) phosphate (TCPP), is ubiquitous in environmental matrices; however, there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of TCPP exposure on zebrafish neurodevelopment and swimming behavior to elucidate the underlying molecular mechanisms of neurotoxicity. Under TCPP gradient concentration exposure, the hatching rates were declined by up to 33.3% in 72 hpf, and the malformation rates increased from 15% to 50%. Meanwhile, TCPP led to abnormal behaviors including decreased locomotive activity in the dark and slow/insensitive responses to sound and light stimulation of larvae. TCPP caused excessive apoptosis and ROS accumulation in early embryonic development, with hair cell defects and structural deformity of neuromast. Abnormal expression of neurodevelopment (pax6a, nova1, sox11b, syn2a, foxo3a and robo2) and apoptosis-related genes (baxa, bcl2a and casp8) revealed molecular mechanisms regarding abnormal behavioral and phenotypic symptoms. Chronic TCPP exposure led to anxiety-like behavior and excessive panic, lower capacity for discrimination and risk avoidance, and conditioned place preference in adults. Social interaction tests demonstrated that long-term TCPP stress resulted in unsociable, eccentric, lonely and silent behaviors in adults. Zebrafish memory and cognitive function were severely reduced as concluded from T-maze tests. Potential mechanisms triggering behavioral abnormality were attributed to histopathological injury of diencephalon, abnormal changes in nerve-related genes at transcription and expression levels, and inhibited activity of AChE by TCPP stress. These findings provide an important reference for risk assessment and early warning to TCPP exposure, and offer insights for prevention/mitigation of pollutant-induced nervous system diseases.
有机磷阻燃剂磷酸三（1-氯-2-丙基）酯（TCPP）广泛存在于环境基质中；然而，有关其全身毒性的信息却很少。在此，我们研究了 TCPP 暴露对斑马鱼神经发育和游泳行为的影响，以阐明其神经毒性的潜在分子机制。在 TCPP 浓度梯度暴露下，72 hpf 时的孵化率下降了高达 33.3%，畸形率从 15%增加到 50%。同时，TCPP 导致了异常行为，包括在黑暗中运动活性降低，以及对声音和光刺激的反应缓慢/不敏感。TCPP 在早期胚胎发育中引起过度凋亡和 ROS 积累，毛细胞缺陷和神经嵴结构畸形。神经发育（pax6a、nova1、sox11b、syn2a、foxo3a 和 robo2）和凋亡相关基因（baxa、bcl2a 和 casp8）的异常表达揭示了异常行为和表型症状的分子机制。慢性 TCPP 暴露导致成年斑马鱼出现焦虑样行为和过度恐慌、辨别力和风险回避能力降低以及条件性位置偏好。社交互动测试表明，长期 TCPP 应激导致成年斑马鱼表现出不合群、异常、孤独和沉默的行为。T 迷宫测试表明，斑马鱼的记忆和认知功能严重受损。导致行为异常的潜在机制归因于间脑的组织病理学损伤、转录和表达水平的神经相关基因的异常变化，以及 TCPP 应激抑制乙酰胆碱酯酶的活性。这些发现为 TCPP 暴露的风险评估和预警提供了重要参考，并为预防/减轻污染物引起的神经系统疾病提供了思路。
