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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21ES013524-01
Application #
6858117
Study Section
Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
Program Officer
Gray, Kimberly A
Project Start
2005-01-01
Project End
2006-11-30
Budget Start
2005-01-01
Budget End
2005-11-30
Support Year
1
Fiscal Year
2005
Total Cost
$196,545
Indirect Cost
Name
University of Cincinnati
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Haynes, Erin N; Sucharew, Heidi; Kuhnell, Pierce et al. (2015) Manganese Exposure and Neurocognitive Outcomes in Rural School-Age Children: The Communities Actively Researching Exposure Study (Ohio, USA). Environ Health Perspect 123:1066-71
Rugless, Fedoria; Bhattacharya, Amit; Succop, Paul et al. (2014) Childhood exposure to manganese and postural instability in children living near a ferromanganese refinery in Southeastern Ohio. Neurotoxicol Teratol 41:71-9
Haynes, Erin N; Beidler, Caroline; Wittberg, Richard et al. (2011) Developing a bidirectional academic-community partnership with an Appalachian-American community for environmental health research and risk communication. Environ Health Perspect 119:1364-72
Haynes, Erin N; Heckel, Pamela; Ryan, Patrick et al. (2010) Environmental manganese exposure in residents living near a ferromanganese refinery in Southeast Ohio: a pilot study. Neurotoxicology 31:468-74
Brubaker, Christopher J; Schmithorst, Vincent J; Haynes, Erin N et al. (2009) Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study. Neurotoxicology 30:867-75
Curran, Christine P; Park, Robert M; Ho, Shuk-mei et al. (2009) Incorporating genetics and genomics in risk assessment for inhaled manganese: from data to policy. Neurotoxicology 30:754-60
Patel, Nick C; DelBello, Melissa P; Cecil, Kim M et al. (2008) Temporal change in N-acetyl-aspartate concentrations in adolescents with bipolar depression treated with lithium. J Child Adolesc Psychopharmacol 18:132-9
Cecil, Kim M; Brubaker, Christopher J; Adler, Caleb M et al. (2008) Decreased brain volume in adults with childhood lead exposure. PLoS Med 5:e112
Standridge, J Shawn; Bhattacharya, Amit; Succop, Paul et al. (2008) Effect of chronic low level manganese exposure on postural balance: a pilot study of residents in southern Ohio. J Occup Environ Med 50:1421-9
Patel, Nick C; Cecil, Kim M; Strakowski, Stephen M et al. (2008) Neurochemical alterations in adolescent bipolar depression: a proton magnetic resonance spectroscopy pilot study of the prefrontal cortex. J Child Adolesc Psychopharmacol 18:623-7

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