Alterations to the circuitry of the frontal cortex following exposure to the polybrominated diphenyl ether mixture, DE-71

• Type of Material: Article
• Authors: Joshua M. Bradner, Emory University; Tiffany A. Suragh, Emory University; William Michael Caudle, Emory University
• Language: English
• Date: 2013-10-04
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 The Authors, Published by Elsevier Ireland Ltd. All rights reserved. CC BY NC ND 4.0
• Final Published Version (URL): http://dx.doi.org/10.1016/j.tox.2013.07.015
• Title of Journal or Parent Work: Toxicology
• ISSN: 0300-483X
• Volume: 312
• Issue: 1
• Start Page: 48
• End Page: 55
• Grant/Funding Information: This work was supported by National Institutes of Health grants [R00ES017477 and P01ES016731 to W.M.C.]
• Keywords: CENTRAL-NERVOUS-SYSTEM; IN-VIVO; PBDES; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Frontal cortex; Toxicology; Science & Technology; GABA; POLYCHLORINATED-BIPHENYLS PCBS; THYROID-HORMONE; Polybrominated diphenyl ethers; GABA(A) RECEPTORS; ADULT MICE; Glutamate; SPONTANEOUS BEHAVIOR; DE-71; NEONATAL EXPOSURE; Cognition; BROMINATED FLAME RETARDANTS
• Research Categories: Environmental Sciences; Biology, Neuroscience

Abstract

Recent studies have identified exposure to polybrominated diphenyl ethers (PBDEs) as a risk factor for deficits in cognitive functioning seen in children as well as adults. Additionally, similar alterations in learning and memory have also been observed in animal models of PBDE exposure. However, given these findings, the molecular alterations that may underlie these neurobehavioral endpoints have not been identified. As the frontal cortex is involved in modulating several cognitive functions, the purpose of our study was to investigate the possible changes to the GABAergic and glutamatergic neurotransmitter systems located in the frontal cortex following exposure to the PBDE mixture, DE-71. Primary cultured neurons isolated from the frontal cortex showed a dose-dependent reduction in neurons as well as neurite outgrowth. Furthermore, evaluation of DE-71 neurotoxicity in the frontal cortex using an in vivo model showed alterations to specific proteins involved in mediating GABA and glutamate neurotransmission, including GAD67, vGAT, vGlut, and GABA(A) 2α receptor subunit. Interestingly, these alterations appeared to be preferential for the GABA and glutamate systems located in the frontal cortex. These findings identify specific targets of PBDE neurotoxicity and provide a possible molecular mechanism for PBDE-mediated neurobehavioral deficits that arise from the frontal cortex.