作为新型有机阻燃剂,氯化有机磷酸酯(Cl-OPEs)具有高水溶性和结构相似性有机磷酸酯农药,对水生生物构成风险。Cl-OPEs的潜在神经毒性引起了人们的关注,尤其是在神经系统相对简单的海洋无脊椎动物中。在这项研究中,一只有脑神经节的海洋轮虫,Brachionusplicatilis,暴露于三(1,3-二氯-2-丙基)磷酸酯(TDCPP)(两种环境浓度和一种极端水平),并探讨了摄食和游泳行为的变化及其内在机理。暴露于1.05nMTDCPP不会改变轮虫的过滤和摄取速率以及平均线速度。但是0.42和4.20μMTDCPP抑制了这三个参数并降低了不饱和脂肪酸含量,繁殖和人口增长。所有TDCPP测试浓度均抑制AChE活性,导致轮虫体内乙酰胆碱的过度积累,从而扰乱电晕纤毛的神经支配。分子对接和分子动力学表明,这种抑制作用是因为TDCPP可以通过范德华力和静电相互作用与轮虫AChE的催化活性位点结合。TRP420是结合中的主要氨基残基,和GLY207有助于氢键。使用LC-MS和GC-MS的非靶向代谢组学鉴定了TDCPP治疗中差异表达的代谢物,主要来自脂质和类脂分子,尤其是鞘脂.TDCPP降低了神经节苷脂含量,但刺激了神经酰胺的产生和与神经酰胺从头合成相关的3个基因的表达水平。线粒体膜电位(MMP)和ATP含量降低,电子呼吸链复合物和TCA循环失活。一种神经酰胺合成酶的抑制剂,伏马尼辛,缓解MMP和ATP,暗示神经酰胺在线粒体功能障碍中的关键作用。因此,TDCPP暴露导致能量供应不足,影响纤毛运动并最终抑制轮虫行为。总的来说,这项研究促进了对海洋无脊椎动物Cl-OPEs神经毒性的认识.
As new organic flame retardants, chlorinated organophosphate esters (Cl-OPEs) have high water solubility and structural similarity to organophosphate pesticides, posing risks to aquatic organisms. The potential neurotoxicity of Cl-OPEs has attracted attention, especially in marine invertebrates with a relatively simple nervous system. In this study, a marine rotifer with a cerebral ganglion, Brachionus plicatilis, was exposed to tris (1,3-dichloro-2-propyl) phosphate (TDCPP) (two environmental concentrations and one extreme level), and the changes in feeding and swimming behaviors and internal mechanism were explored. Exposure to 1.05 nM TDCPP did not change the filtration and ingestion rates of rotifers and average linear velocity. But 0.42 and 4.20 μM TDCPP inhibited these three parameters and reduced unsaturated fatty acid content, reproduction and population growth. All TDCPP test concentrations suppressed AChE activity, causing excessive accumulation of acetylcholine within rotifers, thereby disturbing the neural innervation of corona cilia. Molecular docking and molecular dynamics revealed that this inhibition was because TDCPP can bind to the catalytic active site of rotifer AChE through van der Waals forces and electrostatic interactions. TRP420 was the leading amino residue in the binding, and GLY207 contributed to a hydrogen bond. Nontargeted metabolomics using LC-MS and GC-MS identified differentially expressed metabolites in TDCPP treatments, mainly from lipid and lipid-like molecules, especially sphingolipids. TDCPP decreased ganglioside content but stimulated ceramide generation and the expression levels of 3 genes related to ceramide de novo synthesis. The mitochondrial membrane potential (MMP) and ATP content decreased, and the electron respiratory chain complex and TCA cycle were deactivated. An inhibitor of ceramide synthase, fumonisin, alleviated MMP and ATP, implying a critical role of ceramide in mitochondrial dysfunction. Thus, TDCPP exposure caused an energy supply deficit affecting ciliary movement and ultimately inhibiting rotifer behaviors. Overall, this study promotes the understanding of the neurotoxicity of Cl-OPEs in marine invertebrates.