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：
10883865
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：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10883865
关键词：
Address Adolescent Adolescent and Young Adult Adverse effects Aerosols Affect Air Aldehydes Analytical Chemistry Animal Model Animals Area Authorization documentation Blood Brain Calcium Carcinogens Cardiac Myocytes Cardiovascular Diseases Cardiovascular system Cell Culture Techniques Cell model Cessation of life Characteristics Chromium Chronic Cigarette Clinical Cognition Cognitive deficits Copper Corpus striatum structure Cotinine Data Devices Disease Disease model Dose Electronic cigarette Environmental Engineering technology Epidemiology Etiology Exhibits Exposure to Flavoring General Population Genetic Determinism Genetic Predisposition to Disease Glycerol Health Health Hazards Heating Human Image Impaired cognition Individual Inductively Coupled Plasma Mass Spectrometry Inhalation Iron Knock-in Knowledge LRRK2 gene Laboratories Lead levels Length Link Liquid substance Manganese Measures Mediating Metal exposure Metals Motor Mus Mutation Nerve Degeneration Neurites Neurodegenerative Disorders Neurons Neurotoxins Nickel Nicotine Parkinson Disease Pathologic Patients Perception Phase Policy Maker Predisposition Propylene Glycols Public Health Recording of previous events Reporting Research Personnel Respiratory Disease Risk Role Sampling Selenium Smoker Smoking Solvents Synapses System Testing Tobacco Toxic effect Vanadium Youth Zinc authority base brain health brain tissue cancer risk carcinogenicity density disorder risk dopaminergic neuron e-cigarette aerosols electronic cigarette use electronic cigarette user electronic liquid exposed human population human subject induced pluripotent stem cell motor deficit motor impairment mouse model neurotoxic neurotoxicity novel operation particle premature prevent respiratory secondhand aerosol sporadic Parkinson&apos s Disease tobacco smokers vaping vapor

Address Adolescent Adolescent and Young Adult Adverse effects Aerosols Affect Air Aldehydes Analytical Chemistry Animal Model Animals Area Authorization documentation Blood Brain Calcium Carcinogens Cardiac Myocytes Cardiovascular Diseases Cardiovascular system Cell Culture Techniques Cell model Cessation of life Characteristics Chromium Chronic Cigarette Clinical Cognition Cognitive deficits Copper Corpus striatum structure Cotinine Data Devices Disease Disease model Dose Electronic cigarette Environmental Engineering technology Epidemiology Etiology Exhibits Exposure to Flavoring General Population Genetic Determinism Genetic Predisposition to Disease Glycerol Health Health Hazards Heating Human Image Impaired cognition Individual Inductively Coupled Plasma Mass Spectrometry Inhalation Iron Knock-in Knowledge LRRK2 gene Laboratories Lead levels Length Link Liquid substance Manganese Measures Mediating Metal exposure Metals Motor Mus Mutation Nerve Degeneration Neurites Neurodegenerative Disorders Neurons Neurotoxins Nickel Nicotine Parkinson Disease Pathologic Patients Perception Phase Policy Maker Predisposition Propylene Glycols Public Health Recording of previous events Reporting Research Personnel Respiratory Disease Risk Role Sampling Selenium Smoker Smoking Solvents Synapses System Testing Tobacco Toxic effect Vanadium Youth Zinc authority base brain health brain tissue cancer risk carcinogenicity density disorder risk dopaminergic neuron e-cigarette aerosols electronic cigarette use electronic cigarette user electronic liquid exposed human population human subject induced pluripotent stem cell motor deficit motor impairment mouse model neurotoxic neurotoxicity novel operation particle premature prevent respiratory secondhand aerosol sporadic Parkinson&apos s Disease tobacco smokers vaping vapor

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项目摘要

PROJECT SUMMARY Electronic cigarettes (e-cigs), battery-operated devices that heat liquids to generate an inhaled aerosol vapor, are increasingly popular, especially among younger users. E-cigs are seen as an increasingly attractive alternative to tobacco cigarettes; however, little is known about the human health effects arising from chronic exposure to these aerosols. A growing number of studies have examined potential e-cig risks for cancer, respiratory, and cardiovascular diseases. New data from our laboratory and others, however, raise additional human health concerns about exposure to potentially neurotoxic metals released from the heated coil wire and other e-cig components. For example, we found that in a large fraction e-cig aerosol samples we collected, nickel, chromium, and lead levels exceeded EPA national ambient air quality standards or ATSDR minimum risk levels (MRL). Notably, this was true for manganese (Mn), a prime suspect in sporadic Parkinson’s disease (PD) etiology. Others have found that vanadium, copper and selenium (all suspected for a potential role in PD) were higher in blood of e-cig users as compared to tobacco smokers. We hypothesize that hazardous metals released by e-cigs may accumulate in the brain and pose significant neurotoxic risk(s) for neurodegenerative diseases upon chronic exposure. We will test our hypothesis in three ways. First, we will determine the levels of potentially neurotoxic metals in the aerosol produced by several popular e-cigs operated under different conditions and with e-liquids differing in flavor and nicotine content. Second, we will examine the neurotoxic effect of chronic e-cig aerosol exposure in neuronal cell cultures derived from human subjects carrying incompletely-penetrant mutations linked to PD or from healthy controls, and identify metal mixtures of particular neurotoxic concern. Third, we will measure metal concentrations in brain tissue of chronically e-cig exposed mice, which are wildtype controls or knock-in for a mutation that increases the risk for PD; we will also determine the metals’ potential adverse effects on motor function and cognition in the mouse models. Findings from this study are likely to provide crucial and heretofore unavailable information to policy makers and will enable them to evaluate potential neurotoxic health risks arising from second-hand exposure to e-cig aerosol. We hypothesize that health risks are significantly influenced by genetic susceptibility to neurodegenerative disease, as well as by e-cig device construction, operating conditions, e-liquid flavoring, and nicotine content.

项目摘要电子卷烟（电子烟），电池式设备，加热液体以产生遗传的气溶胶蒸气，越来越受欢迎，尤其是在年轻用户中。电子烟被视为越来越吸引人替代烟草香烟；但是，关于慢性产生的人类健康影响知之甚少暴露于这些气溶胶。越来越多的研究检查了潜在的癌症的潜在电子烟风险，呼吸道和心血管疾病。但是，来自我们实验室和其他人的新数据提出了额外的数据人类健康对暴露于加热线圈线释放的潜在神经毒性金属和其他E-CIG组件。例如，我们发现在收集的大量E-cig气溶胶样品中，镍，铬和铅水平超过EPA国家环境空气质量标准或ATSDR最低风险水平（MRL）。值得注意的是，对于零星帕金森氏病的主要嫌疑人锰（MN）是正确的（PD）病因。其他人发现钒，铜和硒（所有人都怀疑在PD中发挥了潜在作用）我们假设那种危险的金属电子烟可能会积聚在大脑中，并对神经退行性造成显着的神经毒性风险长期暴露时疾病。我们将以三种方式检验我们的假设。首先，我们将确定水平在不同的电子烟中生产的气溶胶中潜在的神经毒性金属的条件以及电子液体在风味和尼古丁含量上有所区分。其次，我们将检查神经毒性慢性电子烟气暴露在携带人类受试者的神经元细胞培养物中的影响与PD或健康对照相关的不完全渗透剂突变，并确定特定的金属混合物神经毒性关注。第三，我们将测量慢性电子烟暴露的脑组织中的金属关注小鼠是野生型对照或敲入突变，会增加PD的风险；我们也会确定金属对小鼠模型中运动功能和认知的潜在不利影响。发现从这项研究中，可能会向政策制定者提供至关重要的不可用的信息，并将使他们能够评估二手暴露于E-CIG气溶胶引起的潜在神经毒性健康风险。我们假设健康风险受到神经退行性的遗传敏感性的显着影响疾病以及通过电子烟设备的建设，工作条件，电子液体调味料和尼古丁含量。