Sensory Mechanisms of Cadmium-Induced Behavioral Disorders Across Generations

项目概要/摘要 一个需要探索的领域是环境引起的行为障碍。研究表明，镉（Cd）毒性可以 表现为人类的行为障碍，认知挑战和视力缺陷，但这些疾病的途径 副作用未知。其漫长的生物半衰期加剧了了解早期生活中的镉是如何 接触会影响到以后的生活结果和后代。在这项研究中，迪利亚谢尔顿博士建议测试 假设慢性人类饮食相关的镉暴露导致视觉行为障碍，在以后的生活和跨 代在K99指导阶段，她将使斑马鱼暴露于慢性人类相关饮食镉浓度 并测试不良的视觉行为影响，然后将这种行为毒性与神经生理学和遗传学联系起来， 终点（目标1）。这建立在她以前开发自动化技术以评估环境特征的基础上 影响野生和家养斑马鱼的社会行为。她将在发展方面提高她的知识， 分子毒理学、神经科学和生物信息学用于暴露、评估和分析镉诱导的 通过教学指导、研讨会， 会议，广泛的实践培训，以及由受人尊敬的研究人员组成的多元化咨询委员会的指导。这 多方面的培训计划将补充她在行为生态学方面的专业知识，为她提供以下方面的新技能： 毒理学研究设计，2）电生理学，以评估镉对视觉和中枢神经系统的影响，3） 用于鉴定遗传终点的分子方法和生物信息学，以及4）用于鉴定， 量化污染物在组织中的积累。在R 00阶段，迪利亚谢尔顿博士将启动新的 研究镉引起的代际和跨代行为障碍。在她的基础上 从K99阶段开始，她将确定新的行为、生理和遗传终点， 代际和跨代行为障碍（目标2）。这些研究的结果将改善我们的 了解膳食镉暴露与视觉行为之间关系的机制 跨代疾病，并进一步阐明环境诱导的行为疾病的病因。表征 视觉行为，视觉和中枢神经系统功能，以及基因表达在饮食镉暴露的背景下， 对减少镉暴露的预防政策有影响。该提案提供了一种替代模式， 迎接现代化学筛选的挑战，更好地解释环境引起的行为障碍。与 在这项拟议的研究中，谢尔顿博士处于有利地位，可以利用现有资源开发独立的，但 补充项目，旨在帮助填补我们对镉对行为影响的理解中的关键空白 这些疾病可能对精神病的公共卫生产生深远影响。

Project Summary/Abstract An area of needed exploration is environmentally-induced behavioral disorders. Studies show Cadmium (Cd) toxicity can manifest as behavioral disorders, cognitive challenges, and vision deficiencies in humans, but the pathway for these adverse effects is unknown. Its long biological half-life exacerbates the importance of understanding how early-life Cd exposure impacts later life outcomes and future generations. In this study, Dr. Delia Shelton proposes to test the hypothesis that chronic human dietary-relevant Cd exposure leads to visuo-behavioral disorders later in life and across generations. In the K99 mentored phase, she will expose zebrafish to chronic human-relevant dietary Cd concentrations and test for adverse visuo-behavioral effects, and then link this behavioral toxicity to neurophysiological and genetic endpoints (aim 1). This builds on her previous work developing automated technologies to assess environmental features that influence social behavior in wild and domestic zebrafish. She will advance her knowledge in developmental molecular toxicology, neuroscience, and bioinformatics used to expose, assess, and analyze the impact of Cd-induced behavioral disorders on behavior, brain, visual physiology and gene expression, through didactic instruction, seminars, conferences, extensive hands-on training, and guidance from a diverse advisory committee of respected researchers. This multifaceted training plan will complement her expertise in behavioral ecology by providing her with new skills in: 1) toxicology study design, 2) electrophysiology to assess the Cd’s impact on visual and central nervous systems, 3) molecular methods and bioinformatics used to identify genetic endpoints, and 4) advanced imaging methods to identify, quantify the accumulation of pollutants in tissues. In the R00 phase, Dr. Delia Shelton will initiate a new line of investigation to examine Cd-induced intergenerational and transgenerational behavioral disorders. By building on her training from the K99 phase she will identify novel behavioral, physiological, and genetic endpoints that predict intergenerational and transgenerational behavioral disorders (aim 2). Findings from these studies will improve our understanding of the mechanisms underlying the relationship between dietary cadmium exposure and visuo-behavioral disorders across generations and further elucidate environment-induced behavioral disease etiology. Characterizing the visuo-behavior, visual and central nervous system function, and gene expression in the context of dietary Cd exposure, has implications for prevention policy directed at reducing Cd exposure. The proposal provides an alternative model to meet modern challenges in chemical screening that better account for environment-induced behavioral disorders. With this proposed study, Dr. Shelton is well positioned to take advantage of existing resources to develop independent, yet complementary projects, designed to help fill critical gaps in our understanding of the impacts of Cd on behavioral disorders that may have far-reaching public health implications for psychiatric pathologies.