Motor and Cognitive Health Outcomes in a Mn-Exposed African Community

接触锰的非洲社区的运动和认知健康结果

• 批准号: 9115153
• 负责人: Brad A Racette
• 金额: $ 52.82万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115153
• 关键词: Adult; Adverse effects; African; Age; Behavior assessment; Behavioral; Black race; Clinical assessments; Cognitive; Communities; Complex; Data; Dose; Environmental Exposure; Environmental Pollution; Epidemiology; Exposure to; Functional disorder; Goals; Health; High Prevalence; Life; Link; Manganese; Modeling; Moods; Motor; Neurotoxins; Outcome; Parkinson Disease; Parkinsonian Disorders; Participant; Pathway interactions; Pharmacology; Phenotype; Plants; Policies; Population; Prevalence; Public Health; Race; Research; Risk; Role; Severities; South Africa; South African; Testing; Trace Elements; United States; United States Environmental Protection Agency; Work; cognitive control; disturbance in affect; epidemiology study; motor disorder; neuropsychological; neurotoxicity; population based; presynaptic; racial difference; response

 DESCRIPTION (provided by applicant): Manganese (Mn) is an established neurotoxicant with complex pharmacology, due to its role as an essential trace element. This proposal builds on a large body of research generated by our investigative team over the last decade. In these studies, we have demonstrated that: Mn-exposed welders have a high prevalence of parkinsonism compared to a reference population; the phenotype of parkinsonism in Mn-exposed workers overlaps substantially with the phenotype seen in Parkinson disease (PD); Mn-exposed workers have presynaptic dopaminergic dysfunction, thereby linking Mn exposure to the same pathways involved in PD; and there is an increased risk of PD in regions of the U.S. with high industrial Mn emissions. In this proposal, we will perform a population-based epidemiology study of Mn-exposed adults living near a large Mn smelter in Meyerton, South Africa, and of a non-exposed reference community in Kroonstad, South Africa, in which we will compare the prevalence and severity of motor, cognitive control, and mood dysfunction between the two communities. Within the Mn-exposed Meyerton community, we will also investigate the dose-response relationship between environmental Mn exposure and these health outcomes. Our preliminary data clearly support the hypotheses we propose to test and demonstrate that the proposed work is feasible. Our research team is ideally suited to conduct these studies and includes world experts in clinical assessment of Mn neurotoxicity, environmental pollution modeling, and epidemiology. The mixed-race (black and white) South African community to be studied will provide a unique opportunity to investigate racial differences to sensitivity to Mn. Demonstrating motor and cognitive health effects from ambient Mn at exposure levels below the current Environmental Protection Agency lowest observed adverse effect level will have a substantial public health impact by informing environmental regulatory policy in the United States and worldwide.

 描述（由适用提供）：锰（MN）是一种具有复杂药理学的神经毒性，因为它是必不可少的痕量元素。该提案建立在过去十年来调查团队产生的大量研究的基础上。在这些研究中，我们已经证明：与参考人群相比，帕金森氏症患病率很高；帕金森氏症工人中帕金森氏症的表型与帕金森氏病（PD）中的表型显着重叠。暴露于MN的工人患有突触前多巴胺能功能障碍，从而将MN暴露与PD相同的途径联系起来。而且，在美国地区高级MN排放量高的美国地区，PD的风险增加了。在这项建议中，我们将对居住在南非梅耶顿的大型MN冶炼厂附近的MN暴露成年人以及南非克鲁恩斯塔德的非暴露参考社区进行基于人群的流行病学研究，我们将在其中比较两个社区之间运动，认知控制和情绪功能障碍的流行和严重性。在公平的Meyerton社区中，我们还将调查环境MN暴露与这些健康结果之间的剂量反应关系。我们的初步数据显然支持我们提出的测试假设，并证明拟议的工作是可行的。我们的研究团队非常适合进行这些研究，并包括有关MN神经毒性，环境污染建模和流行病学的临床评估的世界专家。曾研究的混合种族（黑白）南非社区将提供一个独特的机会，以调查对MN敏感性的种族差异。通过向当前环境保护局低于当前环境保护局的暴露水平的运动和认知健康效应，最低观察到的不利影响水平将通过告知美国和全球环境监管政策，从而产生重大的公共卫生影响。