Biochemical Mechanisms of Olfactory Injury in Salmon

三文鱼嗅觉损伤的生化机制

• 批准号: 9149245
• 负责人: EVAN P GALLAGHER
• 金额: $ 43.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9149245
• 关键词: Abbreviations; Address; Adenylate Cyclase; Adult; Antioxidants; Area; Basal Cell; Behavioral; Biochemical; Biological Markers; Bromodeoxyuridine; Cadmium; Chemical Injury; Chemicals; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communities; Copper; County; Cyclic AMP; Defect; Development; Dose; Ecology; Environment; Environmental Pollutants; Epithelium; Event; Exposure to; Fisheries; Fishes; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic Models; Genomics; Glutathione S-Transferase; Goals; Hazardous Waste; Health; Health Hazards; Home environment; Homing; Human; Immunohistochemistry; Impairment; In Situ Hybridization; Induction of Apoptosis; Inductively Coupled Plasma Mass Spectrometry; Injury; Keratin; Laboratory Study; Life; Link; Mass Spectrum Analysis; Mediating; Metal exposure; Metals; MicroRNAs; Modeling; Molecular; Natural regeneration; Neurologic; Neurons; Olfactory Epithelium; Olfactory Pathways; Olfactory Receptor Neurons; Oncorhynchus kisutch; Organophosphates; Outcome; Oxidative Stress; Pacific Northwest; Peripheral; Peripheral Nervous System; Pesticides; Physiological; Population; Post-Transcriptional Regulation; Protein Isoforms; Proteins; Recovery; Recovery of Function; Regulator Genes; Research Activity; Risk; Role; Salmon; Scanning Electron Microscopy; Sensory; Signal Recognition Particle; Signal Transduction; Signal Transduction Induction; Site; Smell Perception; Staging; Stem cells; Stream; Superfund; Target Populations; Taurocholic Acid; Testing; Time; Toxic effect; Trace metal; Transgenic Organisms; Translating; Transmission Electron Microscopy; Washington; Work; Zebrafish; adduct; base; carboxylesterase; contaminated seafood; field study; in vivo; innovation; interest; killings; knock-down; molecular marker; neurobehavioral; neurogenesis; neurotoxic; new technology; novel marker; novel strategies; olfactory marker protein; overexpression; pollutant; receptor; remediation; reproductive; response; stem; superfund chemical; superfund site; tool; toxic organophosphate insecticide exposure; toxicant

Project summary Exposure to environmental concentrations of pesticides and metals can cause neurobehavioral changes that influence survival of Pacific salmon. These neurological impacts that arise from central and peripheral nervous system deficits, including inhibition of peripheral olfactory function, may block the ability to detect predators and prey, alter reproductive timing, and interfere with homing to natal streams. The fish peripheral olfactory system is highly vulnerable to the toxic effects of dissolved contaminants due to its direct contact with the aquatic environment. Olfactory injury is now documented in other aquatic species exposed to environmental pollutants, suggesting far-reaching ecological ramifications of this phenomenon. The goal of our project is to understand the mechanisms of chemical-induced olfactory injury in Pacific salmon, and based upon our findings, generate biomarkers of olfactory injury to evaluate the ecological health and remediation outcomes at Superfund sites. Our studies will also use zebrafish, a well-defined genetic model, to better understand the mechanisms of olfactory injury that are relevant to salmon. In the current application, we will continue to integrate molecular, biochemical, physiological, and behavioral endpoints using model metal olfactory toxicants that are relevant to Superfund exposures. This novel approach allows a thorough understanding of mechanisms of chemical-induced olfactory injury in fish. In Aim 1, we will identify olfactory receptor neuron populations that are targets of cadmium (Cd) and address impaired olfactory signaling and neuron regeneration (neurogenesis) as mechanisms of Cd-mediated olfactory injury. In Aim 2, we will investigate transcriptional and post-transcriptional control of olfaction during metal exposures. We will identify functionally-important olfactory microRNAs (miRNAs) and their gene targets that are important regulators of metal-induced olfactory injury. In Aim 3, we will develop olfactory biomarkers generated from our work for field studies at Superfund sites. We will verify and test glutathione S-transferase (GST) isoforms as biomarkers of olfactory injury, and carboxylesterase- organophosphate protein adducts as markers of organophosphate exposures. We will use transgenic zebrafish to evaluate other common, but untested, Superfund metals as olfactory toxicants. We will incorporate our olfactory molecular biomarkers within a multiplex platform to evaluate remediation outcomes in the lower Duwamish waterway, a regional Superfund site at various stages of remediation. We have assembled a strong team of collaborators for this project whose interactions are described in the proposal. We have endeavored to be responsive to SRP objectives by using mechanistic approaches to address health hazards and remediation outcomes at Superfund sites in collaboration with EPA partners involved in Superfund site assessment.

项目概要 暴露于环境浓度的农药和金属会导致神经行为变化， 影响太平洋鲑鱼的生存。这些由中枢和周围神经引起的神经系统影响 系统缺陷，包括外围嗅觉功能的抑制，可能会阻碍检测捕食者和 捕食，改变繁殖时间，并干扰对出生流的归巢。鱼的末梢嗅觉系统是 由于直接与水生生物接触，极易受到溶解污染物的毒性影响 环境。现在，在暴露于环境污染物的其他水生物种中也有嗅觉损伤的记录， 表明这种现象具有深远的生态影响。我们项目的目标是了解 化学引起的太平洋鲑鱼嗅觉损伤的机制，并根据我们的发现，产生 嗅觉损伤的生物标志物，用于评估超级基金地点的生态健康和修复结果。 我们的研究还将使用斑马鱼（一种明确的遗传模型）来更好地了解 与鲑鱼有关的嗅觉损伤。在目前的应用中，我们将继续整合分子、 使用与相关的金属嗅觉毒物模型来确定生化、生理和行为终点 超级基金风险敞口。这种新颖的方法可以全面了解 化学引起的鱼类嗅觉损伤。在目标 1 中，我们将识别嗅觉受体神经元群体 镉 (Cd) 的靶标并解决嗅觉信号受损和神经元再生（神经发生）问题 镉介导的嗅觉损伤的机制。在目标 2 中，我们将研究转录和转录后 金属暴露期间的嗅觉控制。我们将鉴定功能重要的嗅觉 microRNA (miRNA) 及其基因靶标是金属引起的嗅觉损伤的重要调节因子。在目标 3 中，我们将开发 我们在超级基金站点进行实地研究时生成的嗅觉生物标志物。我们将验证并测试 谷胱甘肽 S-转移酶 (GST) 亚型作为嗅觉损伤的生物标志物，以及羧酸酯酶 - 有机磷蛋白加合物作为有机磷暴露的标记。我们将使用转基因斑马鱼 评估其他常见但未经测试的超级基金金属作为嗅觉毒物。我们将把我们的 多重平台内的嗅觉分子生物标志物，用于评估较低的修复结果 杜瓦米什水道，一个处于不同修复阶段的地区超级基金场地。我们集结了强大的 该项目的合作者团队，其交互在提案中进行了描述。我们一直努力 通过使用机械方法解决健康危害和补救措施来响应 SRP 目标 与参与超级基金现场评估的 EPA 合作伙伴合作，在超级基金现场取得成果。