Manganese Exposure and Neurodevelopment in Children

描述(由申请人提供)：许多研究已经确定了接触锰与职业接触工人的运动功能缺陷之间的关系。这项研究表明，锰影响包括中枢神经系统在内的几个器官系统，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)的前额叶皮质和边缘区域的发育。对成年人的人体研究表明，接触锰与认知缺陷和失调的情绪和行为之间存在关联，包括焦虑、易怒、情绪障碍和攻击性。吸入锰可能特别隐蔽，因为从嗅球通过边缘系统到前额皮质的运输是直接的路线。到目前为止，还没有研究检验儿童时期来自工业点源的非职业性环境暴露对运动、认知和行为功能的亚临床影响。考虑到发育中的大脑的脆弱性，儿童时期接触锰是一个主要问题。考虑到年轻人的大脑可塑性更高，及早发现暴露及其影响可能会导致有效的补救措施。因此，建议的R21研究旨在评估儿童早期锰暴露与ECF、运动功能和儿童时期失调行为的关系。儿童将从距离环境锰源已知距离的社区中挑选出来，这些社区靠近钢铁厂，环境空气中的锰接近以前与运动损伤有关的职业暴露水平。将进行生物和环境评估，以确定个人的暴露水平。样本将从出生起就一直存在于这些地点。此外，研究设计将铅等其他金属的共生现象降至最低，统计分析将进一步调整此类影响。因此，这项拟议的研究有可能显著扩展先前关于锰暴露对运动影响的发现，增加敏感的、特定选择的、有针对性的和适合儿童发育的认知和行为测量。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)预防广泛暴露的公共卫生计划，(Ii)早期检测神经毒性的筛查计划，以及(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：这项关于儿童早期环境锰暴露的探索性研究将开始探索锰对暴露儿童群体早期神经功能缺陷的公共卫生意义和影响程度。这项研究可能会刺激未来的大规模研究，产生与认知、学习和行为缺陷相关的社区环境条件的概括性知识。因此，将环境暴露与神经发育影响联系起来的公共卫生和预防计划可能会显著改善儿童的生物、认知和行为功能的完整性，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.