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.

 说明(申请人提供)：锰是一种公认的神经毒物，具有复杂的药理作用，因为它是一种必需的微量元素。这项建议建立在我们的调查团队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：与参考人群相比，接触锰的焊工患帕金森病的几率更高；接触锰的工人患帕金森病的表型与帕金森病(PD)的表型有很大重叠；接触锰的工人具有突触前多巴胺能功能障碍，从而将接触锰与导致帕金森病的相同途径联系在一起；在美国工业锰排放高的地区，患帕金森病的风险增加。在这项提案中，我们将对居住在南非迈耶顿一个大型锰冶炼厂附近的接触锰的成年人和南非克罗恩斯塔德的一个非接触的参考社区进行一项基于人群的流行病学研究，在这项研究中，我们将比较这两个社区之间运动、认知控制和情绪障碍的患病率和严重程度。在接触锰的Meyerton社区内，我们还将调查环境中暴露的锰与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了我们提出的假设，并证明了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，包括临床评估锰神经毒性、环境污染建模和流行病学方面的世界专家。将被研究的南非混合种族(黑人和白人)社区将提供一个独特的机会来调查对MN敏感性的种族差异。通过向美国和世界各地的环境监管政策提供信息，证明环境锰暴露水平低于当前环境保护局观察到的最低不良影响水平对运动和认知健康的影响将对公众健康产生重大影响。