Sensory Mechanisms of Cadmium-Induced Behavioral Disorders Across Generations

镉引起的几代人行为障碍的感觉机制

• 批准号: 10607195
• 负责人: Delia S Shelton
• 金额: $ 4.22万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-09 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10607195
• 关键词: Sensory; Mechanisms; Cadmium; Induced; Behavioral

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.

项目摘要/摘要 一个需要探索的领域是环境诱发的行为障碍。研究表明，镉(Cd)毒性可能 在人类中表现为行为障碍、认知障碍和视力障碍，但这些的途径 不良反应尚不清楚。其漫长的生物半衰期加剧了了解早期生命CD的重要性 暴露会影响以后的生活结果和后代。在这项研究中，Delia Shelton博士建议测试 人类长期接触与饮食相关的镉会导致晚年和以后的视觉行为障碍的假说 几代人。在K99指导阶段，她将把斑马鱼暴露在与人类相关的慢性饮食镉浓度中 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 端点(目标1)。这建立在她之前的工作基础上，开发自动化技术来评估环境特征 影响野生和家养斑马鱼的社会行为。她将提高她在发展方面的知识 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影响 行为障碍对行为、大脑、视觉生理和基因表达的影响，通过教学、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样化咨询委员会的指导。这 多方面的培训计划将通过向她提供以下方面的新技能来补充她在行为生态学方面的专业知识：1) 毒理学研究设计，2)电生理学评估镉对视觉和中枢神经系统的影响，3) 用于识别遗传终点的分子方法和生物信息学，以及4)用于识别的先进成像方法， 量化污染物在组织中的累积。在R00阶段，Delia Shelton博士将启动一系列新的 研究镉引起的代际和跨代行为障碍。通过建立在她的基础上 从K99阶段开始的训练她将识别新的行为、生理和遗传终点，这些终点可以预测 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关系的机制 并进一步阐明环境诱导的行为疾病的病因学。描述了 在饮食镉暴露背景下的视觉行为、视觉和中枢神经系统功能以及基因表达， 对旨在减少镉暴露的预防政策产生影响。该提案提供了一种替代模式 应对化学筛选方面的现代挑战，以更好地解释环境诱导的行为障碍。使用 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 补充性项目，旨在帮助填补我们对CD对行为影响的理解方面的关键空白 可能对精神病理的公共卫生产生深远影响的疾病。

项目成果

Wild Zebrafish Sentinels: Biological Monitoring of Site Differences Using Behavior and Morphology.

• DOI: 10.3390/toxics9070165
• 发表时间: 2021-07-12
• 期刊: Toxics
• 影响因子: 4.6
• 作者: Kelly JR;Shelton SG;Daniel DK;Bhat A;Mondal R;Nipple F;Amro H;Bower ME;Isaac G;McHaney G;Martins EP;Shelton DS
• 通讯作者: Shelton DS

Expanding the landscape of opportunity: Professional societies support early-career researchers through community programming and peer coaching.

• DOI: 10.1037/com0000300
• 发表时间: 2021-11
• 期刊: Journal of comparative psychology (Washington, D.C. : 1983)
• 作者: Shelton DS;Delgado MM;Greenway EVG;Hobson EA;Lackey ACR;Medina-García A;Reinke BA;Trillo PA;Wells CP;Horner-Devine MC
• 通讯作者: Horner-Devine MC

Small increases in group size improve small shoals' response to water flow in zebrafish.

• DOI: 10.1111/jzo.12952
• 发表时间: 2022-04
• 期刊: JOURNAL OF ZOOLOGY
• 影响因子: 2
• 作者: Suriyampola, P. S.;Iruri-Tucker, A. A.;Padilla-Velez, L.;Enriquez, A.;Shelton, D. S.;Martins, E. P.
• 通讯作者: Martins, E. P.

Recreating Wakanda by promoting Black excellence in ecology and evolution.

通过促进生态和进化的黑色卓越来重现Wakanda。

• DOI: 10.1038/s41559-020-1266-7
• 发表时间: 2020-10
• 期刊: Nature ecology & evolution
• 影响因子: 16.8
• 作者: Schell CJ;Guy C;Shelton DS;Campbell-Staton SC;Sealey BA;Lee DN;Harris NC
• 通讯作者: Harris NC

Early life stage transient aristolochic acid exposure induces behavioral hyperactivity but not nephrotoxicity in larval zebrafish.

• DOI: 10.1016/j.aquatox.2021.105916
• 发表时间: 2021-07-18
• 期刊: Aquatic toxicology (Amsterdam, Netherlands)
• 作者: Chen J;Kong A;Shelton D;Dong H;Li J;Zhao F;Bai C;Huang K;Mo W;Chen S;Xu H;Tanguay RL;Dong Q
• 通讯作者: Dong Q