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: 10902600
• 负责人: Delia S Shelton
• 金额: $ 8.29万
• 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: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10902600
• 关键词: Ablation; Achievement; Adolescent; Adverse effects; Advisory Committees; Affect; Animals; Architecture; Area; Behavior; Behavior Disorders; Behavioral; Behavioral Assay; Behavioral Paradigm; Bioinformatics; Biological; Biological Assay; Biological Markers; Brain; Cadmium; Cells; Central Nervous System; Cessation of life; Chemicals; Chronic; Cognitive; Complement; Data; Defect; Development; Dietary Cadmium; Disease; Disruptive Behavior Disorder; Early Intervention; Ecology; Elderly; Electrophysiology (science); Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Epigenetic Process; Etiology; Exposure to; Food; Future Generations; Gene Expression; Gene Expression Profiling; Generations; Genetic; Goals; Half-Life; Health; Heavy Metals; Human; Immunohistochemistry; Impairment; Inductively Coupled Plasma Mass Spectrometry; Ingestion; Instruction; Intake; Intervention; Investigation; Knowledge; Lasers; Learning; Learning Disabilities; Life; Link; Memory; Mental disorders; Mentors; Methods; Modeling; Modernization; Molecular; Molecular Toxicology; National Institute of Environmental Health Sciences; Nervous System Physiology; Neuropsychology; Neurosciences; Ocular Physiology; Outcome; Pathology; Pathway interactions; Perception; Phase; Physiological; Policies; Pollution; Population; Positioning Attribute; Prevention; Public Health; Research; Research Design; Research Personnel; Resources; Retina; Rodent; Role; Sensory; Social Behavior; Social Development; System; Systems Biology; Techniques; Technology; Testing; Tissues; Toxic effect; Toxicology; Training; Transgenic Organisms; Vision; Visual; Visual System; Visual impairment; Water; Work; Zebrafish; age related; antisocial behavior; behavioral impairment; bioinformatics tool; burden of illness; career; cost; design; dietary; disability; environmental stressor; high throughput screening; imaging modality; improved; in vivo; insight; intergenerational; laser capture microdissection; neural; neurocognitive disorder; neuropathology; neurophysiology; neurotoxicity; non-smoking; novel; pollutant; premature; response; screening; sensory mechanism; skills; social; social influence; superior colliculus Corpora quadrigemina; symposium; transcriptome sequencing; visual motor

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 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，认知挑战和视力不足，但这些途径 不良影响未知。它的长期生物半衰期加剧了理解早期CD的重要性 暴露会影响以后的生活成果和子孙后代。在这项研究中，Delia Shelton博士的提议要测试 假设慢性人类饮食中与饮食中的CD暴露会导致生命之后和跨越的视觉行为疾病 几代人。在K99修补阶段，她将使斑马鱼暴露于慢性人类与人与饮食的CD浓度 并测试不良视觉行为效应，然后将这种行为毒性与神经生理和遗传学联系起来 终点（AIM 1）。这是她以前开发自动化技术来评估环境特征的工作的基础 这会影响野生和国内斑马鱼的社会行为。她将提高她的发展知识 用于暴露，评估和分析CD诱导的影响的分子毒理学，神经科学和生物信息学 关于行为，大脑，视觉生理和基因表达的行为障碍，通过教学，半手， 受人尊敬的研究人员的潜水咨询委员会的会议，大量的动手培训和指导。这 多方面的培训计划将通过为她提供新技能：1）来补充她在行为生态学方面的专业知识 毒理学研究设计，2）评估CD对视觉和中枢神经系统的影响的电生理学，3） 用于鉴定遗传终点的分子方法和生物信息学，以及4）高级成像方法，以识别， 量化污染物在组织中的积累。在R00阶段，Delia Shelton博士将启动一条新线 研究以检查CD诱导的代际和转化行为障碍。通过在她身上建造 从K99阶段进行培训，她将确定预测的新型行为，物理和遗传终点 代际和跨代行为障碍（AIM 2）。这些研究的发现将改善我们的 了解饮食镉暴露与视觉行为之间关系的机制 跨世代的疾病，并进一步阐明了环境诱发的行为疾病病因。表征 视觉行为，视觉和中枢神经系统功能以及在饮食CD暴露的背景下的基因表达， 对有针对减少CD暴露的预防政策有影响。该提案为 应对化学筛查中的现代挑战，以更好地说明环境引起的行为障碍。和 这项拟议的研究，谢尔顿博士有能力利用现有资源来发展独立，但 完全项目，旨在帮助填补我们对CD对行为影响的影响的关键空白 可能对精神病病具有深远的公共卫生影响的疾病。

项目成果

A pair of cadmium-exposed zebrafish affect social behavior of the un-exposed majority.

一对接触镉的斑马鱼会影响大多数未接触镉的斑马鱼的社会行为。

• DOI: 10.1016/j.etap.2023.104119
• 发表时间: 2023
• 期刊: Environmental toxicology and pharmacology
• 影响因子: 4.3
• 作者: Shelton,DeliaS;Dinges,ZoeM;Khemka,Anuj;Sykes,DelawrenceJ;Suriyampola,PiyumikaS;Shelton,DoloresEP;Boyd,Ploypenmas;Kelly,JeffreyR;Bower,Myra;Amro,Halima;Glaholt,StephenP;Latta,MitchellB;Perkins,HannahL;Shaw,JosephR;Mar
• 通讯作者: Mar

A Pair of Cadmium-exposed Zebrafish Affect Boldness and Landmark use in the Un-exposed Majority.

一对暴露于镉的斑马鱼会影响大多数未暴露于镉的斑马鱼的胆量和地标性使用。

• DOI: 10.1101/2023.11.09.566440
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Shelton,DeliaS;Suriyampola,PiyumikaS;Dinges,ZoeM;Glaholt,StephenP;Shaw,JosephR;Martins,EmíliaP
• 通讯作者: Martins,EmíliaP