The goal of this work is to begin to identify biological mechanisms that contribute to neurocognitive deficits in children exposed to low-level lead. This research plan proposes to measure blood lead levels in a large population of minority and underserved children;compare neurocognitive functioning in children with and without detectable blood lead levels;and examine associations between selected genetic polymorphisms and neurocognitive performance in children exposed to low-level lead. Lead exposure is a significant health disparity. Low-level lead exposure has long been associated with diminished cognitive function, and may pose an unrecognized threat to the cognitive health and well-being of an unknown number of minority and underserved children. Moreover, previously unexamined common genetic differences may potentiate the neurotoxic effects of lead in children. Lead toxicity is diagnosed when a child's blood lead level (BLL) is >10 micrograms per deciliter (g/dL). According to the EPA however, a """"""""Reference Dose"""""""" value, that is a concentration below which no adverse effects have been observed, is not available for lead. In response to over 40 studies showing diminished IQ in children with BLLs <10 g/dL, the CDC convened an expert committee in 2003 to critically examine the findings. The findings were unequivocally confirmed. But in its decision to maintain the 10 g/dL threshold, the committee cited the need for studies suggesting causative biological mechanisms. We do not yet understand the mechanisms by which low-level lead exposure causes neurocognitive decline in young children. This is a critical knowledge gap, which creates the risk of lower cognitive function and diminished quality of life, especially for minority and underserved children. As a result of this gap, child blood lead levels <10.0 g/dL are ignored. Our central hypothesis is that chronic low-level lead exposure impairs neurocognitive function through mechanisms that are genetically mediated. H1: 25% of minority children between the ages of 5 and 12 have """"""""detectable"""""""" blood lead levels (4.0 - 9.9 g/dL);H2: as compared to children with """"""""undetectable"""""""" blood lead levels, children with """"""""detectable"""""""" blood lead levels perform more poorly on neurocognitive tasks associated with brain networks specifically vulnerable to lead;H3: children with """"""""detectable"""""""" blood lead levels, and carrying one or both genetic polymorphisms, have lowest scores on tests of neurocognitive function. Findings from these studies may begin to suggest the numbers of minority and underserved children ages 5 - 12 currently exposed to low-level lead;which types of neurocognitive deficits result;and whether common genetic differences potentiate the neurotoxic effects of lead. The findings may also suggest new avenues for detection, primary prevention and intervention.

Public Health Relevance

Lead exposure is a significant health disparity, low-level lead exposure has been associated with diminished cognitive function, and yet low-level lead exposure continues to be ignored, perhaps posing a hidden threat to the health and well-being of an unknown number of minority and underserved children. Common genetic differences may increase its neurotoxic effects. Findings from these studies may begin to suggest the numbers of currently exposed minority and underserved children ages 5 - 12 years, and which neurocognitive deficits result, while suggesting new avenues for detection and primary prevention.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD060120-02
Application #
7803622
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Oster-Granite, Mary Lou
Project Start
2009-04-09
Project End
2013-05-31
Budget Start
2010-03-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2010
Total Cost
$183,150
Indirect Cost
Name
University of Texas El Paso
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
132051285
City
El Paso
State
TX
Country
United States
Zip Code
79968
Sobin, Christina; Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel (2017) Early chronic low-level Pb exposure alters global exploratory behaviors but does not impair spatial and object memory retrieval in an object-in-place task in pre-adolescent C57BL/6J mice. Neurotoxicol Teratol 61:104-114
Del Rio, Michelle; Alvarez, Juan; Mayorga, Tania et al. (2017) A comparison of arsenic exposure in young children and home water arsenic in two rural West Texas communities. BMC Public Health 17:850
Flores-Montoya, Mayra Gisel; Sobin, Christina (2015) Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice. J Appl Toxicol 35:759-65
Sobin, Christina; Flores-Montoya, Mayra Gisel; Gutierrez, Marisela et al. (2015) ?-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter 2*2 haplotype (hPEPT2*2) differently influence neurobehavior in low-level lead exposed children. Neurotoxicol Teratol 47:137-45
Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina (2015) Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure. Toxicol Lett 236:69-74
Basgen, John M; Sobin, Christina (2014) Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice. Toxicol Lett 225:48-56
Sobin, Christina; Montoya, Mayra Gisel Flores; Parisi, Natali et al. (2013) Microglial disruption in young mice with early chronic lead exposure. Toxicol Lett 220:44-52
Sobin, Christina; Parisi, Natali; Schaub, Tanner et al. (2011) ?-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 and peptide transporter 2*2 haplotype may differentially mediate lead exposure in male children. Arch Environ Contam Toxicol 61:521-9
Sobin, Christina; Parisi, Natali; Schaub, Tanner et al. (2011) A Bland-Altman comparison of the Lead Careýý System and inductively coupled plasma mass spectrometry for detecting low-level lead in child whole blood samples. J Med Toxicol 7:24-32
Sobin, Christina; Gutierrez, Marisela; Alterio, Heather (2009) Polymorphisms of delta-aminolevulinic acid dehydratase (ALAD) and peptide transporter 2 (PEPT2) genes in children with low-level lead exposure. Neurotoxicology 30:881-7