Manganese Exposure and Neurodevelopment in Children

描述（由申请人提供）：许多研究已经确定了职业暴露的工人中锰（Mn）暴露与运动功能缺陷之间的关系。这项研究表明，锰影响几个器官系统，包括中枢神经系统，导致各种神经行为症状。动物研究表明，吸入锰可能会干扰调节人类执行认知功能（ECF）的前额叶皮层和边缘系统区域的发育。对成人的人体研究表明，锰暴露与认知缺陷和情绪和行为失调（包括焦虑、易怒、情绪障碍和攻击性）之间存在关联。锰的吸入可能是特别阴险的，因为直接的运输路线从嗅球通过边缘系统到前额皮质。到目前为止，没有研究探讨了亚临床影响的非职业环境暴露于锰在童年时期从工业点源的运动，认知和行为功能。考虑到发育中的大脑的脆弱性，儿童期暴露于锰是一个主要问题。鉴于年轻人的大脑可塑性更大，早期发现暴露及其影响可能会导致有效的补救措施。因此，拟议的R21研究旨在评估儿童早期锰暴露与ECF、运动功能和儿童期行为失调之间的关系。将从距离环境锰源已知距离的社区中选择儿童，这些社区靠近环境空气锰接近先前与运动损伤相关的职业暴露水平的钢铁米尔斯厂。将进行生物和环境评估，以确定个人接触水平。样本将自出生起就一直留在这些部位。此外，研究设计最大限度地减少了其他金属（如铅）的共存，统计分析将进一步调整此类影响。因此，拟议的研究有可能显着扩大之前的研究结果与锰暴露的运动影响，增加了敏感的，专门选择的，有针对性的，发育适当的认知和行为措施的儿童。对可能暴露于神经毒物的人群进行流行病学监测可能导致（i）公共卫生计划，以防止广泛暴露，（ii）筛查计划，以早期发现神经毒性，（iii）在严重和更永久性的残疾发生之前治疗由此产生的亚临床神经功能障碍。 公共卫生相关性：这项探索性研究的环境暴露于锰在幼儿期将开始，探讨公共卫生的意义和锰的影响程度对早期神经功能缺损的暴露儿童群体。这项研究可能会刺激未来的大规模研究，这将产生与认知，学术和行为缺陷相关的社区环境条件的可推广的知识。因此，将环境暴露与神经发育影响联系起来的研究结果纳入公共卫生和预防计划可能会对儿童的生物，认知和行为功能的完整性产生重大改善，并产生长期影响。

DESCRIPTION (provided by applicant): Numerous studies have established a relationship between manganese (Mn) exposure and motor function deficits in workers who are occupationally exposed. This research suggests that Mn affects several organ systems, including the central nervous system, resulting in a variety of neurobehavioral symptoms. Animal studies indicate that inhalation of Mn may interfere with the development of the prefrontal cortex and limbic regions that modulate executive cognitive function (ECF) in humans. Human studies in adults show an association between Mn exposure and cognitive deficits and dysregulated moods and behaviors, including anxiety, irritability, emotional disturbance, and aggression. Inhalation of Mn may be particularly insidious because of the direct route of transport from the olfactory bulbs through the limbic system to the prefrontal cortex. To date, no study has examined the subclinical effects of nonoccupational ambient exposures to Mn during childhood from industrial point sources on motor, cognitive, and behavioral functions. Childhood exposure to Mn is a primary concern given the vulnerability of the developing brain. Early detection of exposure and its effects may lead to effective remedies given the greater degree of brain plasticity in the young. Thus, the proposed R21 study is designed to assess the relationship between early childhood Mn exposure and ECF, motor function, and dysregulated behavior in childhood. Children will be selected from communities at known distances from environmental Mn sources, proximate to steel mills with ambient air Mn that approaches the level of occupational exposures previously associated with motor impairment. Biological and environmental assessments will be conducted to determine individual levels of exposure. The sample will have resided in these sites since birth. Also, the study design minimizes the co-occurrence of other metals, such as lead, and the statistical analyses will further adjust for such effects. Thus, the proposed study has potential to significantly expand upon prior findings related to motor effects of Mn exposures with the addition of sensitive, specifically selected, targeted, and developmentally appropriate cognitive and behavioral measures in children. Epidemiologic surveillance of populations potentially exposed to neurotoxicants may lead to (i) public health programs to prevent widespread exposures, (ii) screening programs for early detection of neurotoxicity, and (iii) treatment of resultant subclinical neurological dysfunction before severe and more permanent disability occurs. PUBLIC HEALTH RELEVANCE: This exploratory study on environmental exposure to Mn during early childhood will begin to explore the public health significance and magnitude of Mn effects on early neurofunctional deficits in groups of exposed children. The research is likely to stimulate a future large-scale study that will yield generalizable knowledge about environmental conditions of communities associated with cognitive, academic, and behavioral deficits. As a result, public health and prevention programs that incorporate findings linking environmental exposures to neurodevelopmental impacts are likely to produce significant improvements in integrity of biological, cognitive, and behavioral functioning in children with long term implications.