NEUROBEHAVIORAL EFFECTS OF MANGANESE EXPOSURE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 锰（Mn）是一种必需元素，但过量时具有神经毒性。 与不良反应相关的最低锰水平和测量低水平锰暴露的理想生物标志物定义不清。此外，有一些证据表明，锰和铅（铅）的毒性是生物协同作用。一个非侵入性的方法来检测锰暴露在大脑中，其毒性的靶器官，将是非常宝贵的锰神经毒性的研究。 锰很容易穿过血脑屏障，选择性地积累在尾状核和苍白球。 磁共振成像（MRI）可以反映锰在脑内的沉积。 鉴于汽油中锰的使用增加以及低水平铅暴露对健康不利影响的新数据，开展研究以确定锰暴露的合适生物标志物并确定低水平锰暴露对健康的影响至关重要。 我们寻求探索以下具体目标：具体目标1：慢性低水平锰暴露的非侵入性生物标志物。 具体目标二：使用目前公认的暴露生物标志物和MRI生物标志物表征慢性低水平锰暴露的神经行为效应。 具体目标3：使用目前公认的暴露生物标志物和MRI生物标志物表征铅和锰联合暴露的神经行为效应。 辛辛那提铅研究队列是铅暴露儿童中运行时间最长的队列研究，它提供了一个独特的机会，可以检查低水平锰暴露的年轻人大脑中的锰沉积，并对终生铅暴露和神经发育进行广泛测量。如果我们证明，MRI是一个有效的措施，低水平锰暴露和锰暴露预测受损的神经行为功能，那么这项研究将大大推进环境健康研究，并有广泛的影响政策，以控制环境暴露于锰。

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.