NEUROBEHAVIORAL EFFECTS OF MANGANESE EXPOSURE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。锰是一种必需元素，但过量的锰具有神经毒性。与不良反应相关的最低锰水平和衡量低水平锰暴露的理想生物标记物定义不明确。此外，有证据表明，锰和铅(铅)在毒性方面具有生物协同作用。一种非侵入性的检测脑内锰暴露的方法对于研究锰的神经毒性将是非常有价值的。锰很容易通过血脑屏障，选择性地聚集在尾状核和苍白球中。磁共振成像(MRI)可以反映锰在大脑中的沉积。鉴于汽油中锰使用量的增加以及关于低水平铅暴露对健康不利影响的新数据，开展研究以确定适当的锰暴露生物标志物和确定低水平锰暴露对健康的影响至关重要。我们试图探索以下特定目标：特定目标1：验证慢性、低水平锰暴露的非侵入性生物标志物。具体目标2：使用目前公认的暴露生物标记物和MRI生物标记物来表征慢性低水平锰暴露的神经行为影响。具体目标3：使用目前公认的暴露生物标记物和MRI生物标记物来表征铅和锰联合暴露的神经行为影响。辛辛那提铅研究队列是对铅暴露儿童进行时间最长的队列研究，它提供了一个独特的机会来检查低水平锰暴露的年轻人大脑中的锰沉积，以及对终生铅暴露和神经发育的广泛测量。如果我们证明MRI是低水平锰暴露的有效手段，并且锰暴露预测神经行为功能受损，那么这项研究将极大地促进环境健康研究，并对控制环境中锰暴露的政策具有广泛的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Manganese (Mn) is an essential element, but it is neurotoxic in excess. The lowest level of Mn associated with adverse effects and the ideal biomarker for measuring low-level Mn exposure is poorly defined. Moreover, there is some evidence that Mn and lead (Pb) are biologically synergistic in their toxicity. A noninvasive method of detecting Mn exposure in the brain, its target organ of toxicity, would be invaluable for the study of Mn neurotoxicity. Mn readily crosses the blood-brain-barrier, selectively accumulating in the caudate and the globus pallidus. Magnetic resonance imaging (MRI) can reflect Mn deposition in the brain. Given the increased use of Mn in gasoline and the emerging data on adverse health effects of low-level Pb exposure, it is critical to conduct studies to identifying a suitable biomarker of Mn exposure and to identify the health effects of low-level Mn exposure. We seek to explore the following specific aims: Specific Aim 1: Validate a noninvasive biomarker of chronic, low-level Mn exposure. Specific Aim 2: Characterize the neurobehavioral effects of chronic, low-level Mn exposure using currently accepted biomarkers of exposure and a MRI biomarker. Specific Aim 3: Characterize the neurobehavioral effects of combined exposure to Pb and Mn using currently accepted biomarkers of exposure and a MRI biomarker. The Cincinnati Lead Study cohort, the longest running cohort study of Pb exposed children, provides a unique opportunity to examine Mn deposition in the brain of young adults with low-level Mn exposure and extensive measures of lifetime Pb exposure and neurological development. If we demonstrate that MRI is a valid measure of low-level Mn exposure and Mn exposure predicts impaired neurobehavioral functions, then this study will substantially advance environmental health research and have broad implications for policy to control environmental exposure to Mn.