The maturation of the central nervous system requires a complex sequence of processes over an extended period of time, making this organ particularly vulnerable to environmental influences. The long term behavioral morbidities associated with prenatal and postnatal exposures to environmental chemicals remain uncertain. We also lack data on direct anatomical evidence of neurological damage resulting from lower level exposures to known developmental neurotoxicants. We have very little information on how genotypic variances may function as exacerbating or protective factors in neurodevelopmental morbidity. In the area of children's environmental health there has never been a systematic attempt to 1) Determine the impact of early exposure on behavior in later adulthood;2) Identify the specific neuroanatomical substrates and physiological processes that may have sustained damage as well as their neuropsychological correlates in behavior;and 3) Assess interactions between genes encoding proteins involved in neurotransmitter molecular functions and environmental exposures in the expression of neuroanatomical anomalies, and behavioral problems. In this study, we will examine the relationship between prenatal and postnatal exposure to lead (Pb), concurrent exposure to manganese and neuroanatomical anomalies measured non- invasively using magnetic resonance imaging the spectroscopy (MRI/MRS), adult attention deficit hyperactivity disorder (A-ADHD) and related co-morbidities as well as criminal behavior in subjects in their mid 20s. Another goal of this study is to examine these dose-response relationships in the context of genotypic variances related to dopaminergic and serotonergic function in the central nervous system. The proposed research builds on a longstanding prospective study of subjects recruited prenatally beginning in 1979 who continue to be followed today. The Cincinnati Lead Study (CIS) cohort is predominantly African- American with a history of socioeconomic disadvantages. Out of an initial cohort of 305 subjects we continue to track approximately 250 in their early 20s. Exposure to Pb has been assessed serially in blood from the first trimester to 17 years of age. We will be assessing concurrent Mn exposure in blood as well as in brain using an innovative MRI-derived biomarker as a possible modifier of lead's long lasting effects on neurobehavior. There is a rich database covering the cohort's lifespan medical and social histories.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES015559-04
Application #
7799321
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Gray, Kimberly A
Project Start
2007-06-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
4
Fiscal Year
2010
Total Cost
$297,743
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
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VanDuyn, Natalia; Nass, Richard (2014) The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans. J Neurochem 128:962-74
VanDuyn, Natalia; Settivari, Raja; LeVora, Jennifer et al. (2013) The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration. J Neurochem 124:147-57
Settivari, Raja; VanDuyn, Natalia; LeVora, Jennifer et al. (2013) The Nrf2/SKN-1-dependent glutathione S-transferase ? homologue GST-1 inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of manganism. Neurotoxicology 38:51-60
Cecil, Kim M (2013) Proton magnetic resonance spectroscopy: technique for the neuroradiologist. Neuroimaging Clin N Am 23:381-92
Rudgalvyte, Martina; VanDuyn, Natalia; Aarnio, Vuokko et al. (2013) Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans. Toxicol Lett 222:189-96
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Cecil, Kim M; Dietrich, Kim N; Altaye, Mekibib et al. (2011) Proton magnetic resonance spectroscopy in adults with childhood lead exposure. Environ Health Perspect 119:403-8
Brubaker, Christopher J; Dietrich, Kim N; Lanphear, Bruce P et al. (2010) The influence of age of lead exposure on adult gray matter volume. Neurotoxicology 31:259-66
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

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