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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结