The overall goal of the FRIENDS Children's Environmental Health Center is to understand the impact of? prenatal exposure to contaminants found in fish-including polychlorinated biphenyls (PCBs),? polybrominated diphenyl ethers (PBDEs) and methyl mercury (MeHg)-on cognitive, motor and auditory? function of children. The animal studies described in this proposal will complement a parallel prospective? birth cohort study (Project 2) in which children born to women consuming fish contaminated with these? chemicals will be followed longitudinally from birth. The animal studies will'use an experimental PCB mixture? that mimics the PCB congener profile in the fish consumed by women in the epidemiological study. One? major goal is to elucidate the effects of PCBs and PBDEs on important executive processes including? attention and inhibitory control. Drug challenges with methylphenidate and amphetamine will determine if? commonly prescribed ADHD pharmacotherapies improve the performance of PCB- or PBDE-exposed rats? on tests of attention and response inhibition, and measures of DA D4 and DA D1 receptor expresion and? drug challenges using specific DA D4 and DA D1 receptor agonists will indicate whether these receptor? pathways are involved in mediating the behavioral effects. These studies will be conducted in parallel with? another laboratory study (Project 4) which will investigate the effects of PCB and PBDE exposure on central? catecholamine function and the extent to which these effects are mediated indirectly through PCB or PBDE? effects on circulating thyroid hormones. A second major goal is to understand the mechanisms through? which PCBs damage the cohclea and produce hearing loss. Histological examinations of the cochlea will? confirm whether hearing deficits are due to outer hair cell damage. The contribution of reductions in? circulating thyroid hormones or alterations in ryanodine receptor expression in the cochlea to PCB-induced? hearing loss will be investigated by utilizing two specific PCB congeners having opposing effects on thyroid? hormones and ryanodine channel activity. Because the outer hair cells are believed to protect against noise? induced hearing loss, studies will also be conducted to determine if early PCB exposure increases? susceptibility to noise-induced hearing loss later in life. As in the past, findings from these animal studies will? guide the selection of outcome measures for use in the birth cohort.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES015687-03
Application #
7447885
Study Section
Special Emphasis Panel (ZES1-LKB-A (C1))
Program Officer
Kirshner, Annette G
Project Start
2006-09-20
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$292,458
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Monaikul, Supida; Eubig, Paul; Floresco, Stan et al. (2017) Strategy set-shifting and response inhibition in adult rats exposed to an environmental polychlorinated biphenyl mixture during adolescence. Neurotoxicol Teratol 63:14-23
Bandara, Suren B; Sadowski, Renee N; Schantz, Susan L et al. (2017) Developmental exposure to an environmental PCB mixture delays the propagation of electrical kindling from the amygdala. Neurotoxicology 58:42-49
Sadowski, Renee N; Stebbings, Kevin A; Slater, Bernard J et al. (2016) Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABAA antagonism. Neurotoxicology 56:86-93
Bandara, Suren B; Eubig, Paul A; Sadowski, Renee N et al. (2016) Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus. Toxicol Sci 149:335-45
Poon, Emily; Bandara, Suren B; Allen, Jont B et al. (2015) Developmental PCB exposure increases susceptibility to audiogenic seizures in adulthood. Neurotoxicology 46:117-24
Eubig, Paul A; Noe, Terese E; Floresco, Stan B et al. (2014) Sex differences in response to amphetamine in adult Long-Evans rats performing a delay-discounting task. Pharmacol Biochem Behav 118:1-9
Poon, Emily; Monaikul, Supida; Kostyniak, Paul J et al. (2013) Developmental exposure to polychlorinated biphenyls reduces amphetamine behavioral sensitization in Long-Evans rats. Neurotoxicol Teratol 38:6-12
Paule, Merle G; Green, Leonard; Myerson, Joel et al. (2012) Behavioral toxicology of cognition: extrapolation from experimental animal models to humans: behavioral toxicology symposium overview. Neurotoxicol Teratol 34:263-73
Sable, Helen J K; Monaikul, Supida; Poon, Emily et al. (2011) Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs). Neurotoxicol Teratol 33:255-62
Poon, Emily; Powers, Brian E; McAlonan, Ruth M et al. (2011) Effects of developmental exposure to polychlorinated biphenyls and/or polybrominated diphenyl ethers on cochlear function. Toxicol Sci 124:161-8

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