Impairment in the mesohippocampal dopamine circuit following exposure to the brominated flame retardant, HBCDD

• Type of Material: Article
• Authors: Camille Pham-Lake, Emory University; Elizabeth B. Aronoff, Emory University; Chaad R. Camp, Emory University; Aimee Vester, Emory University; Sam J. Peters, Emory University; William Michael Caudle, Emory University
• Language: English
• Date: 2017-03-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.etap.2017.02.003
• Title of Journal or Parent Work: Environmental Toxicology and Pharmacology
• ISSN: 1382-6689
• Volume: 50
• Start Page: 167
• End Page: 174
• Grant/Funding Information: This work was supported by National Institutes of Health grants R00 ES017477 (WMC) and a pilot award awarded to WMC through P30 ES019776
• Keywords: Environmental Sciences; SYNAPTIC PLASTICITY; POLYBROMINATED DIPHENYL ETHERS; Hippocampus; DENTATE GYRUS; HEXABROMOCYCLODODECANE HBCD; Dopamine transporter; Life Sciences & Biomedicine; Hexabromocyclododecane; Substantia nigra pars compacta; Pharmacology & Pharmacy; WISTAR RATS; Tyrosine hydroxylase; Toxicology; HIPPOCAMPAL-FORMATION; ALPHA-SYNUCLEIN; Vesicular monoamine transporter 2; Environmental Sciences & Ecology; NEONATAL EXPOSURE; PARKINSONS-DISEASE; LONG-TERM POTENTIATION; Science & Technology
• Research Categories: Health Sciences, General; Environmental Sciences; Health Sciences, Public Health

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.