Exposure to the polybrominated diphenyl ether mixture DE-71 damages the nigrostriatal dopamine system: Role of dopamine handling in neurotoxicity

Autor: Hye Mi Kim, Kristen A. Stout, Gary W. Miller, Douglas I. Walker, W. Wyatt Wilson, W. Michael Caudle, Joshua M. Bradner, Tiffany A. Suragh, Min Z. Wang, Carlos R. Lazo, Kurt D. Pennell, Jason R. Richardson
Rok vydání: 2013
Předmět:
medicine.medical_specialty
Chromatography
Gas
3
4-Dihydroxyphenylacetic acid
Tyrosine 3-Monooxygenase
Dopamine
Dopamine Plasma Membrane Transport Proteins
Cell Count
Mice
Transgenic
Substantia nigra
Motor Activity
Transfection
Vesicular monoamine transporter 2
Article
Mice
chemistry.chemical_compound
Polybrominated diphenyl ethers
Developmental Neuroscience
Mesencephalon
Internal medicine
Halogenated Diphenyl Ethers
medicine
Animals
Humans
Cells
Cultured
Chromatography
High Pressure Liquid
reproductive and urinary physiology
Neurons
Analysis of Variance
Dose-Response Relationship
Drug
biology
Pars compacta
Homovanillic acid
Homovanillic Acid
Corpus Striatum
Endocrinology
Neurology
chemistry
Biochemistry
Vesicular Monoamine Transport Proteins
biology.protein
3
4-Dihydroxyphenylacetic Acid
Neurotoxicity Syndromes
medicine.drug
Zdroj: Experimental Neurology. 241:138-147
ISSN: 0014-4886
DOI: 10.1016/j.expneurol.2012.12.013
Popis: In the last several decades polybrominated diphenyl ethers (PBDEs) have replaced the previously banned polychlorinated biphenyls (PCBs) in multiple flame retardant utilities. As epidemiological and laboratory studies have suggested PCBs as a risk factor for Parkinson's disease (PD), the similarities between PBDEs and PCBs suggest that PBDEs have the potential to be neurotoxic to the dopamine system. The purpose of this study was to evaluate the neurotoxic effects of the PBDE mixture, DE-71, on the nigrostriatal dopamine system and address the role of altered dopamine handling in mediating this neurotoxicity. Using an in vitro model system we found DE-71 effectively caused cell death in a dopaminergic cell line as well as reducing the number of TH+ neurons isolated from VMAT2 WT and LO animals. Assessment of DE-71 neurotoxicity in vivo demonstrated significant deposition of PBDE congeners in the brains of mice, leading to reductions in striatal dopamine and dopamine handling, as well as reductions in the striatal dopamine transporter (DAT) and VMAT2. Additionally, DE-71 elicited a significant locomotor deficit in the VMAT2 WT and LO mice. However, no change was seen in TH expression in dopamine terminal or in the number of dopamine neurons in the substantia nigra pars compacta (SNpc). To date, these are the first data to demonstrate that exposure to PBDEs disrupts the nigrostriatal dopamine system. Given their similarities to PCBs, additional laboratory and epidemiological research should be considered to assess PBDEs as a potential risk factor for PD and other neurological disorders.
Databáze: OpenAIRE
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