Neurotoxicity and gene expression alterations in zebrafish larvae in response to manganese exposure.
Neurotoxicity and gene expression alterations in zebrafish larvae in response to manganese exposure.
复制标题
斑马鱼幼虫对锰暴露的神经毒性和基因表达变化。
DOI：
10.1016/j.scitotenv.2022.153778
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发表时间：
2022-02
期刊：
影响因子：
--
通讯作者：
Meng X
中科院分区：
文献类型：
--
作者：
Xu Y;Peng T;Xiang Y;Liao G;Zou F;Meng X
锰（Mn）是一种必需的微量元素，但过量暴露会损害精神，认知和运动功能。虽然许多研究报道了锰的毒性，但其潜在机制仍不清楚。在这里，野生型和/或Tg（NBT：DsRed）斑马鱼胚胎/幼体暴露于不同剂量的锰，以确定对死亡率，畸形率和孵化率的影响。利用视频跟踪系统对斑马鱼幼鱼的运动行为进行了研究。采用末端脱氧核苷酸转移酶dUTP缺口末端标记法和吖啶橙子染色法检测细胞凋亡，免疫组化法检测多巴胺转运体和酪氨酸羟化酶（TH）的表达。同时，对斑马鱼仔鱼头部组织进行转录组测序，寻找锰神经毒性的分子靶点。结果表明，锰暴露可增加斑马鱼幼鱼的死亡率和畸形率，并显著降低游泳距离和速度。此外，凋亡的多巴胺能神经元的比例增加，而TH的表达显着下降。转录组测序结果显示，大量与细胞凋亡和DNA损伤修复相关的差异表达基因上调，与上述结果一致。同时，Western blot分析表明，高浓度锰暴露可诱导MAPK通路的激活。这些数据表明，锰暴露可以损伤多巴胺能神经元，并引起细胞凋亡，这对斑马鱼幼虫的运动能力有不利影响。
Manganese (Mn) is an essential trace element, but excessive exposure can damage mental, cognitive, and motor functions. Although many studies have reported the toxicity of Mn, the underlying mechanism remains unclear. Here, wild-type and/orTg(NBT:DsRed)zebrafish embryos/larvae were exposed to different dosages of Mn to determine the effects on mortality, malformation, and hatching rates. A video tracking system was used to analyze the locomotor activities of zebrafish larvae. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and acridine orange staining were performed to monitor cell apoptosis, while dopamine transporter and tyrosine hydroxylase (TH) expression were detected by immunohistochemical staining. Meanwhile, transcriptome sequencing of the head tissues of zebrafish larvae was performed to search for molecular targets of Mn neurotoxicity. The results showed that Mn exposure increased the mortality and malformation rates of zebrafish larvae, and significantly reduced swim distance and velocity. In addition, the proportion of apoptotic dopaminergic neurons increased, while TH expression significantly decreased. The results of transcriptome sequencing showed that a large number of differentially expressed genes associated with apoptosis and DNA damage repair were upregulated, consistent with the above results. Meanwhile, Western blot analysis showed that higher exposure level of Mn could induce activation of MAPK pathway. These data demonstrate that Mn exposure can damage dopaminergic neurons and cause apoptosis, which has detrimental effects on the motor abilities of zebrafish larvae.