Calcium signaling as a possible mechanism behind increased locomotor response in zebrafish larvae exposed to a human relevant persistent organic pollutant mixture or PFOS
Calcium signaling as a possible mechanism behind increased locomotor response in zebrafish larvae exposed to a human relevant persistent organic pollutant mixture or PFOS
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DOI：
10.1016/j.envres.2020.109702
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发表时间：
2020-08-01
影响因子：
8.3
通讯作者：
Kamstra, Jorke H.
中科院分区：
文献类型：
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作者：
Christou, Maria;Fraser, Thomas W. K.;Kamstra, Jorke H.
持久性有机污染物广泛存在于环境中，其生物累积性可对许多生物体的健康产生不利影响。以前，使用斑马鱼作为脊椎动物模型，我们发现幼虫暴露于29种基于斯堪的纳维亚人口平均血液水平的持久性有机污染物的混合物中，表现出过度活跃，并确定全氟辛烷磺酸（PFOS）为行为变化的驱动剂。为了确定可能的机制，我们暴露斑马鱼幼虫从6至96小时后受精到相同的混合物的持久性有机污染物在两个浓度或一个单一的全氟辛烷磺酸暴露（0.55和3.83亩M），并进行行为测试和转录组学分析。暴露的斑马鱼幼体的行为改变包括活动过度，并证实了先前报告的结果。转录组学分析表明，上调的转录相关的肌肉收缩，是高度调节的肌浆网中的钙的可用性。抗毒性途径分析表明，在接触持久性有机污染物混合物和全氟辛烷磺酸的幼虫中，受影响的途径之一是通过激活兰尼碱受体（RyR）发出钙信号。RyR抑制剂和行为结果的功能分析证实了这些发现。受影响的其他途径与接触较低浓度全氟辛烷磺酸的幼虫的脂质代谢有关。通过使用组学技术，我们观察到暴露的斑马鱼幼虫的行为模式改变可能直接由影响肌肉功能的机制控制，而不是通过与神经毒性相关的机制。
Persistent organic pollutants (POPs) are widespread in the environment and their bioaccumulation can lead to adverse health effects in many organisms. Previously, using zebrafish as a model vertebrate, we found larvae exposed to a mixture of 29 POPs based on average blood levels from the Scandinavian population showed hyperactivity, and identified perfluorooctanesulfonic acid (PFOS) as the driving agent for the behavioral changes. In order to identify possible mechanisms, we exposed zebrafish larvae from 6 to 96 h post fertilization to the same mixture of POPs in two concentrations or a single PFOS exposure (0.55 and 3.83 mu M) and performed behavioral tests and transcriptomics analysis. Behavioral alterations of exposed zebrafish larvae included hyperactivity and confirmed previously reported results. Transcriptomics analysis showed upregulation of transcripts related to muscle contraction that is highly regulated by the availability of calcium in the sarcoplasmic reticulum. Ingenuity pathway analysis showed that one of the affected pathways in larvae exposed to the POP mixture and PFOS was calcium signaling via the activation of the ryanodine receptors (RyR). Functional analyses with RyR inhibitors and behavioral outcomes substantiate these findings. Additional pathways affected were related to lipid metabolism in larvae exposed to the lower concentration of PFOS. By using omics technology, we observed that the altered behavioral pattern in exposed zebrafish larvae may be controlled directly by mechanisms affecting muscle function rather than via mechanisms connected to neurotoxicity.