title: Impairment in the mesohippocampal dopamine circuit following exposure to the brominated flame retardant, HBCDD.
abstract: Many chemicals have been used to increase the safety of consumer products by reducing their flammability and risk for ignition. Recent focus on brominated flame retardants, such as polybrominated diphenyl ethers (PBDEs) has shown them to contribute to neurobehavioral deficits in children, including learning and memory. As the manufacture and use of PBDEs have been reduced, replacement chemicals, such as hexabromocyclododecane (HBCDD) have been substituted. Our current study evaluated the neurotoxicity of HBCDD, concentrating on dopaminergic innervation to the hippocampus. Using an in vivo model, we exposed male mice to HBCDD and then assessed alterations to the dopamine synapse 6 weeks later. These exposures elicited significant reductions in presynaptic dopaminergic proteins, including TH, COMT, MAO-B, DAT, VMAT2, and alpha-synuclein. In contrast, postsynaptic dopamine receptors were not impaired. These findings suggest that the mesohippocampal dopamine circuit is vulnerable to HBCDD and the dopamine terminal may be a selective target for alteration.
authors.affiliation: Department of Environmental Health, Rollins School of Public Health Emory University, Atlanta, GA 30322-3090, USA.
authors.forename: Camille
authors.initials: C
authors.lastname: Pham-Lake
authors.affiliation: Department of Environmental Health, Rollins School of Public Health Emory University, Atlanta, GA 30322-3090, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Aronoff
authors.affiliation: Department of Environmental Health, Rollins School of Public Health Emory University, Atlanta, GA 30322-3090, USA.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Camp
authors.affiliation: Department of Environmental Health, Rollins School of Public Health Emory University, Atlanta, GA 30322-3090, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Vester
authors.affiliation: Department of Environmental Health, Rollins School of Public Health Emory University, Atlanta, GA 30322-3090, USA.
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Peters
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: William.m.caudle@emory.edu.
authors.forename: W Michael
authors.initials: WM
authors.lastname: Caudle
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects*; D005411:Flame Retardants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008297:Male; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D055366:Synaptic Potentials / Q000187:drug effects; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D051844:alpha-Synuclein; C089796:hexabromocyclododecane
keywords: Dopamine transporter; Hexabromocyclododecane; Hippocampus; Substantia nigra pars compacta; Tyrosine hydroxylase; Vesicular monoamine transporter 2