Pham-Lake Camille, Aronoff Elizabeth B, Camp Chad R, Vester Aimee, Peters Sam J, Caudle W Michael
Department of Environmental Health, Rollins School of Public Health Emory University, Atlanta, GA 30322-3090, USA.
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.
Environ Toxicol Pharmacol. 2017 Mar;50:167-174. doi: 10.1016/j.etap.2017.02.003. Epub 2017 Feb 4.
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.
许多化学物质已被用于通过降低消费品的可燃性和着火风险来提高其安全性。最近对溴化阻燃剂的关注，如多溴二苯醚（PBDEs），已表明它们会导致儿童神经行为缺陷，包括学习和记忆方面。随着多溴二苯醚的生产和使用减少，已被替代化学品，如六溴环十二烷（HBCDD）所取代。我们目前的研究评估了六溴环十二烷的神经毒性，重点关注海马体的多巴胺能神经支配。使用体内模型，我们将雄性小鼠暴露于六溴环十二烷，然后在6周后评估多巴胺突触的变化。这些暴露导致突触前多巴胺能蛋白显著减少，包括酪氨酸羟化酶（TH）、儿茶酚-O-甲基转移酶（COMT）、单胺氧化酶-B（MAO-B）、多巴胺转运体（DAT）、囊泡单胺转运体2（VMAT2）和α-突触核蛋白。相比之下，突触后多巴胺受体未受损。这些发现表明，中脑-海马多巴胺回路易受六溴环十二烷影响，多巴胺终端可能是其改变的一个选择性靶点。
