Low-dose methylmercury exposure impairs the locomotor activity of zebrafish: role of intestinal inositol metabolism.
Low-dose methylmercury exposure impairs the locomotor activity of zebrafish: role of intestinal inositol metabolism.
复制标题
低剂量甲基汞暴露损害斑马鱼的运动活动：肠道肌醇代谢的作用。
DOI：
10.1016/j.envres.2020.110020
复制
发表时间：
2020-08
影响因子：
8.3
通讯作者：
J. Zhu;Lei Tang;Shanlei Qiao;Lijuan Wang;Yiming Feng;Li Wang;Qian Wu;P. Ding;Zhan Zhang-Zhan-Zha
中科院分区：
文献类型：
--
作者：
J. Zhu;Lei Tang;Shanlei Qiao;Lijuan Wang;Yiming Feng;Li Wang;Qian Wu;P. Ding;Zhan Zhang-Zhan-Zha
甲基汞（MeHg）是一种普遍存在的具有神经毒性作用的环境毒物。尽管对其神经毒性的研究较多，但肠道菌群的作用仍不清楚。在本研究中，成年斑马鱼和幼斑马鱼分别以0、1和10 ng/mL的剂量暴露于甲基丙烯酸甲酯中。甲基甲基氯暴露通过上调脑细胞凋亡和自噬相关基因来损害运动活性。肠道和大脑代谢组学表明，成年斑马鱼暴露后，磷脂酰肌醇信号系统和肌醇磷酸代谢途径受到显著影响。肠和脑肌醇（MI）水平下降，呈正相关。成年斑马鱼的16s rRNA测序数据显示，甲基氯暴露还改变了肠道微生物群的结构，降低了拟杆菌门和变形菌门的相对丰度，进一步在属水平上鉴定为气单胞菌和鲸杆菌。进一步的功能分析表明，MeHgCl破坏了肠道微生物群的肌醇磷酸代谢。值得注意的是，补充心肌可恢复运动活动损伤，并抑制凋亡和自噬相关基因（如asbcl-2和atg5）的上调。因此，本研究不仅揭示了肠道微生物群在mehgcl介导的神经毒性中的关键作用，而且为拮抗其毒性提供了新的见解。
Methylmercury (MeHg) is a ubiquitous environmental toxicant with neurotoxic effects. Although its neurotoxicity had been more studied, the role of gut microbiota remains unclear. In this study, adult zebrafish and larvae were exposed to MeHgCl at the dose of 0, 1 and 10 ng/mL. MeHgCl exposure impaired the locomotor activity via upregulation of apoptosis and autophagy related genes in the brain. Intestinal and cerebral metabolome indicated that phosphatidylinositol signaling system and inositol phosphate metabolism pathways were significantly impacted in adult zebrafish upon MeHgCl exposure. The levels of myo-inositol (MI) in the intestine and brain were decreased and positively correlated. 16 S rRNA sequencing data from adult zebrafish showed that MeHgCl exposure also shifted the structure of gut microbiota and reduced the relative abundance ofBacteroidetesandProteobacteria, which were further identified at genus level asAeromonasandCetobacterium. Further functional analysis indicated that MeHgCl disrupted inositol phosphate metabolism of gut microbiota. Notably, MI supplementation restored the impairment of locomotor activity and inhibited the upregulation of apoptosis and autophagy related genes, such asbcl-2andatg5. Thus, this study not only revealed the key role of gut microbiota in MeHgCl-mediated neurotoxicity but also gave new insights into antagonizing its toxicity.