title: Alterations to the circuitry of the frontal cortex following exposure to the polybrominated diphenyl ether mixture, DE-71.
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.
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322-3090, USA; Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, GA 30322-3090, USA. Electronic address: joshua.m.bradner@emory.edu.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Bradner
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Suragh
authors.forename: W Michael
authors.initials: WM
authors.lastname: Caudle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005411:Flame Retardants / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C086401:pentabromodiphenyl ether
keywords: Cognition; DE-71; Frontal cortex; GABA; Glutamate; Polybrominated diphenyl ethers
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