Jason R. Richardson, Ph.D., Gary W. Miller, Ph.D., William Michael Caudle, Ph.D.
University of Medicine and Dentistry-New Jersey/Robert Wood Johnson Medical School, Emory University
NIEHS Grants R01ES015991, P30ES005022, R00ES017477, P01ES016731, T32ES012870
Findings from an NIEHS-funded study point to polybrominated diphenyl ethers (PBDEs) as a possible risk factor for Parkinson’s disease and other neurodegenerative diseases.
PBDEs are used as flame retardants and are chemically similar to PCBs, which studies have suggested can increase risk for Parkinson's disease. To see if PBDEs are also neurotoxic, the researchers evaluated the in vivo and in vitro effects of PBDE mixture DE-71. Previous research showed that vesicular monoamine transporter 2 (VMAT2) mediates dopamine neuron vulnerability and can be inhibited by PBDEs. Thus, they were particularly interested in studying how deficits in VMAT2 expression and function might influence the neurotoxicity of DE-71.
The investigators found that DE-71 caused cell death in a dopamine-secreting cell line and also lowered the number of dopamine-secreting neurons isolated from mice that expressed normal amounts of VMAT2, as well as from mice that expressed approximately 5 percent of normal VMAT2 levels. Mice exposed to DE-71 had significant deposits of PBDE congeners in their brains, reductions in locomotor activity, and less dopamine in the area of the brain associated with Parkinson’s disease. These changes were worse in animals deficient in VMAT2. The researchers conclude that their findings warrant additional laboratory and epidemiological research on PBDEs as a potential risk factor for Parkinson’s disease and other neurological disorders.
Citation: Bradner JM, Suragh TA, Wilson WW, Lazo CR, Stout KA, Kim HM, Wang MZ, Walker DI, Pennell KD, Richardson JR, Miller GW, Caudle WM. 2013. Exposure to the polybrominated diphenyl ether mixture DE-71 damages the nigrostriatal dopamine system: Role of dopamine handling in neurotoxicity. Exp Neurol 241:138-147.