Abstract：
Global water bodies are now at risk from inevitable cyanobacterial blooms and their production of multiple cyanotoxins, in particular cylindrospermopsin (CYN). However, research on the CYN toxicity and its molecular mechanisms is still limited, whilst the responses of aquatic species against CYN are uncovered. By integrating behavioral observations, chemical detections and transcriptome analysis, this study demonstrated that CYN exerted multi-organ toxicity to model species, Daphnia magna. The present study confirmed that CYN could cause protein inhibition by undermining total protein contents, and altered the gene expression related to proteolysis. Meantime, CYN induced oxidative stress by increasing reactive oxygen species (ROS) level, decreasing the glutathione (GSH) concentration, and interfered with protoheme formation process molecularly. Neurotoxicity led by CYN was solidly determined by abnormal swimming patterns, reduced acetylcholinesterase (AChE), and downward expression of muscarinic acetylcholine receptor (CHRM). Importantly, for the first time, this research determined CYN directly interfered with energy metabolism in cladocerans. CYN distinctively reduced filtration and ingestion rate by targeting on heart and thoracic limbs, which declined the energy intake, and could be further displayed by the reduction of motional strength and the trypsin concentration. These phenotypic alterations were supported by transcriptomic profile, including the down-regulation of oxidative phosphorylation and ATP synthesis. Moreover, CYN was speculated to trigger the self-defense responses of D. magna, known as \"abandon-ship\" by moderating lipid metabolism and distribution. This study, overall, comprehensively demonstrated the CYN toxicity and the responses of D. magna against it, which is of great significance to the advancements of CYN toxicity knowledge.
摘要：
全球水体现在面临不可避免的蓝藻水华及其产生多种蓝藻毒素的风险，特别是圆柱精蛋白（CYN）。然而,关于CYN毒性及其分子机制的研究仍然有限，同时揭示了水生物种对CYN的反应。通过整合行为观察，化学检测和转录组分析，这项研究表明，CYN对模型物种具有多器官毒性，大型水蚤.本研究证实，CYN可以通过破坏总蛋白质含量来引起蛋白质抑制，并改变了与蛋白水解相关的基因表达。同时,CYN通过增加反应性氧化物质（ROS）水平诱导氧化应激，降低谷胱甘肽（GSH）浓度，并在分子上干扰了原血红素的形成过程。CYN导致的神经毒性是由异常的游泳模式确定的，减少的乙酰胆碱酯酶（AChE），毒蕈碱型乙酰胆碱受体(CHRM)的下调表达。重要的是,第一次,这项研究确定CYN直接干扰锁骨的能量代谢。CYN通过靶向心脏和胸部肢体显著降低过滤和摄食率，减少了能量的摄入，并且可以通过运动强度和胰蛋白酶浓度的降低进一步显示。这些表型改变得到了转录组学的支持，包括氧化磷酸化和ATP合成的下调。此外，据推测，CYN会触发D.magna的自卫反应，通过调节脂质代谢和分布被称为“弃船”。这项研究,总的来说,全面展示了CYN的毒性和D.magna对它的反应，这对CYN毒性知识的进步具有重要意义。
