Mechanisms of nitrogen excretion, toxicity and tolerance in ancient and modern fishes

古代和现代鱼类的氮排泄、毒性和耐受性机制

• 批准号: 194686-2010
• 负责人: Wilkie, Michael
• 金额: $ 1.97万
• 依托单位: Wilfrid Laurier University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506426
• 关键词: Mechanisms; nitrogen; excretion; toxicity; tolerance

The overarching aim of my research is to determine how fishes produce and excrete nitrogenous wastes (N-wastes) such as ammonia and urea, and how they cope with potentially toxic build-ups of these products. The breakdown of excess amino acids generates neurotoxic ammonia that must either be excreted or converted to less toxic wastes such as urea. Although ammonia targets the central nervous system (CNS), its precise mechanism of toxicity is unresolved. Blood and CNS ammonia may reach toxic concentrations due to liver failure in mammals. In fishes, internal ammonia increases following feeding, and when excretion by the gill is prevented by altered water chemistry (e.g. > water pH) or elevated water ammonia arising from natural (e.g. decomposition of organic material) or anthropogenic sources (e.g. sewage effluent, agricultural run-off). I propose to determine how N-waste excretion systems in fishes are influenced by feeding and life-stage, and to identify the underlying mechanisms of ammonia toxicity and tolerance. Sea lampreys will be the model for studying excretion. My previous work demonstrated that feeding profoundly stimulated ammonia and urea excretion in parasitic lampreys as they fed on the blood of sharks and trout, making them ideal for learning more about the mechanisms and evolution of N-waste excretion strategies in vertebrates. Goldfish and trout will be used to determine how the CNS of fishes copes with build-ups of ammonia when excretion is impaired or after feeding. My objectives for the next 5 years will be to: (i) determine how ammonia and urea transport systems are altered during the lamprey life-cycle and by feeding, (ii) identify the mechanisms of acute ammonia toxicity and tolerance in the CNS of goldfish and more ammonia-sensitive trout, and (iii) ascertain how feeding and prolonged sub-lethal ammonia exposure affect the ammonia-tolerance and CNS of goldfish and trout. The integrative approach I will use will include whole animal models, cultured brain cells, molecular techniques, and electrophysiology. This research will answer fundamental questions on the mechanisms and evolution of waste excretion in vertebrates, and it may identify novel mechanisms of ammonia tolerance in fish.

我研究的首要目标是确定鱼类如何产生和排泄含氮废物（氮废物），例如氨和尿素，以及它们如何应对这些产品的潜在有毒积累。 过量氨基酸的分解会产生神经毒性氨，必须将其排出体外或转化为毒性较小的废物，例如尿素。尽管氨以中枢神经系统（CNS）为目标，但其确切的毒性机制尚未解决。 由于哺乳动物的肝功能衰竭，血液和中枢神经系统的氨可能达到有毒浓度。在鱼类中，摄食后体内氨会增加，并且当水化学成分改变（例如 > 水 pH）或自然来源（例如有机物质分解）或人为来源（例如污水、农业废水）导致水氨升高而阻止鳃排泄时，体内氨会增加。径流）。我建议确定鱼类的氮废物排泄系统如何受到摄食和生命阶段的影响，并确定氨毒性和耐受性的潜在机制。海七鳃鳗将成为研究排泄物的模型。我之前的工作表明，当寄生七鳃鳗以鲨鱼和鳟鱼的血液为食时，喂食会极大地刺激它们的氨和尿素排泄，这使它们成为了解脊椎动物氮废物排泄策略的机制和进化的理想选择。金鱼和鳟鱼将用于确定鱼类的中枢神经系统在排泄受损或进食后如何应对氨的积累。我未来 5 年的目标是：(i) 确定七鳃鳗生命周期中氨和尿素运输系统如何通过进食而改变，(ii) 确定金鱼中枢神经系统急性氨毒性和耐受性的机制以及更多对氨敏感的鳟鱼，以及 (iii) 确定摄食和长期亚致死氨暴露如何影响金鱼和鳟鱼的氨耐受性和中枢神经系统。我将使用的综合方法将包括整个动物模型、培养脑细胞、分子技术和电生理学。这项研究将回答有关脊椎动物废物排泄机制和进化的基本问题，并可能确定鱼类氨耐受的新机制。