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: 8975835
• 负责人: Brad A Racette
• 金额: $ 55.96万
• 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/8975835
• 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; 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; public health relevance; 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（由申请方提供）：锰（Mn）是一种公认的神经毒物，具有复杂的药理学作用，因为它是一种必需的微量元素。这一建议建立在我们的调查小组在过去十年中进行的大量研究的基础上。在这些研究中，我们已经证明：锰暴露的焊工有一个高流行率的帕金森综合征相比，参考人群;帕金森综合征的表型在锰暴露工人的重叠与帕金森病（PD）的表型，锰暴露的工人有突触前多巴胺能功能障碍，从而连接锰暴露到相同的途径参与PD;并且在具有高工业Mn排放的美国区域中存在增加的PD风险。在本提案中，我们将对居住在南非梅耶顿一家大型锰冶炼厂附近的锰暴露成年人和南非克龙斯塔德的一个非暴露参考社区进行一项基于人群的流行病学研究，其中我们将比较两个社区之间运动、认知控制和情绪功能障碍的患病率和严重程度。在锰暴露的梅耶顿社区，我们还将调查环境锰暴露和这些健康结果之间的剂量反应关系。我们的初步数据清楚地支持我们提出的假设，以测试和证明所提出的工作是可行的。我们的研究团队非常适合进行这些研究，包括锰神经毒性临床评估，环境污染建模和流行病学方面的世界专家。混合种族（黑人和白色）南非社区进行研究将提供一个独特的机会，调查种族差异的敏感性锰。通过告知美国和全球的环境监管政策，证明环境锰在低于当前环境保护局最低观察到的不良影响水平的暴露水平下对运动和认知健康的影响将对公共健康产生重大影响。