Manganese Exposure and Neurodevelopment in Children

描述（由申请人提供）：许多研究已经建立了锰（Mn）暴露与职业暴露工人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）的前额皮质和边缘区域的发育。成人人体研究显示，锰暴露与认知缺陷、情绪和行为失调（包括焦虑、易怒、情绪障碍和攻击）之间存在关联。Mn的吸入可能特别危险，因为从嗅球通过边缘系统直接运输到前额皮质。迄今为止，还没有研究调查了儿童时期工业点源的非职业环境锰暴露对运动、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。考虑到年轻人大脑可塑性更强，早期发现暴露及其影响可能会导致有效的补救措施。因此，R21研究旨在评估儿童早期锰暴露与ECF、运动功能和儿童行为失调之间的关系。儿童将从距离环境锰源已知距离的社区中选择，这些社区靠近钢铁厂，其环境空气中锰的含量接近先前与运动障碍相关的职业暴露水平。将进行生物和环境评估，以确定个人接触水平。样本从出生起就一直在这些地方。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这种影响。因此，该研究有可能在先前研究结果的基础上，通过增加敏感的、专门选择的、有针对性的、适合儿童发育的认知和行为措施，显著扩展锰暴露对运动的影响。对潜在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）筛选计划，以早期发现神经毒性，以及（iii）在发生严重和更永久性残疾之前治疗由此产生的亚临床神经功能障碍。

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.