This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
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National Center for Research Resources Initial Review Group (RIRG)
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Cincinnati Children's Hospital Medical Center
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