Neurotoxic and neurodegenerative risks from chronic exposure to metal mixtures in e-cigarette aerosol

长期接触电子烟气溶胶中的金属混合物会产生神经毒性和神经退行性风险

• 批准号: 10600594
• 负责人: Markus Hilpert
• 金额: $ 7.32万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10600594
• 关键词: Adverse effects; Affect; Animal Model; Animals; Area; Behavioral; Biological Markers; Biology; Blood; Blood Circulation; Brain; Brain Diseases; Cells; Chronic; Cognition; Cognitive; Cognitive deficits; Communication; Copper; Corpus striatum structure; Data; Deposition; Disease; Disease model; Dose; Electronic cigarette; Enrollment; Environmental Exposure; Environmental Health; Environmental Science; Evaluation; Exposure to; GLAST Protein; Genetic Predisposition to Disease; Haitian; Hand; Homeostasis; Human; Impairment; In Vitro; Individual; Inhalation; Intervention Studies; Iron; Knock-in; Knowledge; LRRK2 gene; Laboratory Research; Lead; Lead levels; Link; Manganese; Master of Science; Measures; Membrane; Mentors; Mentorship; Metal exposure; Metals; Minor; Monitor; Mus; Mutation; Nerve Degeneration; Neural Cell Adhesion Molecule L1; Neurodegenerative Disorders; Organ; Parkinson Disease; Pathologic; Pathway interactions; Peripheral; Prevention; Public Health Schools; Reporting; Research; Research Training; Risk; Role; Schools; Science; Statistical Data Interpretation; Strontium; Students; Surface; Testing; Toxicology; Training; Travel; Universities; base; black women; brain cell; brain pathway; capsule; career; college; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; experience; experimental study; extracellular vesicles; falls; gene environment interaction; metal metabolism; motor deficit; neurotoxic; neurotoxicity; novel; novel marker; parent grant; potential biomarker; programs; skills; skills training; toxic metal; vaper; working group

Project summary The main objective of this project is to investigate the feasibility of using a novel peripheral biomarker—the metal cargo of circulating brain-derived extracellular vesicles (EVs)—to assess non-invasively metal deposition in brain due to e-cigarette aerosol exposure. This project is a supplement to an ongoing R01, which investigates the neurotoxic, behavioral and pathological consequences of metal exposure and metal dyshomeostasis in mice exposed to e-cigarette aerosol. The candidate for this supplement is a US citizen of Haitian descent. She graduated from Barnard College with a B.A. degree in Environmental Science and a minor in Biology. Her enrollment into our MS program at Columbia University in the Fall of 2022 will increase the representation of Black women in science, which is particularly lacking. For her research and training, she will be mentored by Drs. Diane Re and Markus Hilpert, MPIs of the parent grant, and she will receive additional mentorship from Dr. Ana Navas-Acien who is part of the e-cigarette working group at Columbia University. In the proposed project, the candidate will (1) determine whether metal content in blood brain-EVs is a longitudinal biomarker of e-cigarette exposure and brain metal elimination upon exposure to e-cigarette aerosol, (2) investigate whether brain EV metal levels can be used to non-invasively infer metal burden in the brain of e-cigarette exposed mice, and (3) explore whether genetic susceptibility to Parkinson's disease (PD) modifies brain EV metal content. Through the proposed analyses, the candidate will gain experience and skills in: 1) the use of novel EV biomarkers to study the effects of metal exposure from e-cigarette use on neurodegenerative disease, 2) statistical analysis of the novel biomarker data; 3) training in animal models of environmental exposures, and 4) understanding the mechanisms of toxic metal exposure from e-cigarette use on metal homeostasis in the brain and neurodegenerative disease. The candidate will also receive formal training by taking courses through our MS program during the regular school year. The candidate and mentors will meet once a week for training and to discuss progress. This project could validate the first brain-relevant peripheral biomarker to predict brain metal load of subjects exposed to e-cigarette aerosol. Based on this study, brain EV metal load could become an established biomarker of individual neurotoxic risk for vapers and second-hand exposure. The proposed research has also significant implications for intervention studies to reduce adverse effects of e-cigarette aerosol exposure. Finally, by providing advanced skills, training and laboratory research opportunities to a Master of Science student with focus in toxicology, this project will enhance diversity in our research team at Columbia University and down the road in the fields of toxicology and environmental health sciences.

项目概要 该项目的主要目标是研究使用新型外周生物标志物——金属 循环脑源性细胞外囊泡（EV）的货物——评估大脑中的非侵入性金属沉积 该项目是对正在进行的 R01 的补充，该项目调查了电子烟气溶胶暴露。 小鼠金属暴露和金属稳态失调的神经毒性、行为和病理后果 暴露于电子烟气溶胶。 该补助金的候选人是一位海地裔美国公民，她毕业于巴纳德学院。 她拥有环境科学学士学位，辅修生物学。 哥伦比亚大学将于 2022 年秋季增加黑人女性在科学领域的代表性，这是 对于她的研究和培训，她将得到 Diane Re 博士和 Markus Hilpert 博士的指导。 家长资助的 MPI，她还将获得 Ana Navas-Acien 博士的额外指导，她是 哥伦比亚大学电子烟工作组在拟议项目中，候选人将 (1) 确定 血脑电动汽车中的金属含量是否是电子烟暴露和脑金属的纵向生物标志物 暴露于电子烟气溶胶后消除，(2) 研究脑 EV 金属水平是否可用于 非侵入性推断电子烟暴露小鼠大脑中的金属负担，以及（3）探索遗传是否 对帕金森病 (PD) 的易感性会改变大脑 EV 金属含量。 通过所提出的分析，候选人将获得以下方面的经验和技能：1）使用新型电动汽车 研究电子烟使用中金属暴露对神经退行性疾病影响的生物标志物，2) 新生物标志物数据的统计分析；3) 环境暴露动物模型的训练，以及 4) 了解电子烟使用中有毒金属暴露对大脑金属稳态的影响机制 候选人还将通过参加我们的课程接受正式培训。 MS项目在正常学年期间将每周举行一次培训和导师会议。 讨论进展。 该项目可以验证第一个与大脑相关的外周生物标志物来预测受试者的脑金属负荷 根据这项研究，暴露于电子烟气溶胶中的脑部 EV 金属负荷可能成为一个既定的生物标志物。 拟议的研究也具有重要意义。 最后，通过干预研究减少电子烟气溶胶暴露的不利影响。 为理学硕士生提供先进的技能、培训和实验室研究机会 专注于毒理学，该项目将增强我们哥伦比亚大学及整个研究团队的多样性 毒理学和环境健康科学领域的道路。