Selective damage to dopaminergic transporters following exposure to the brominated flame retardant, HBCDD

Over the last several decades, the use of halogenated organic compounds
has become the cause of environmental and human health concerns. Of
particular notoriety has been the establishment of the neurotoxicity of
polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers
(PBDEs). The subsequent banning of PBDEs has led to greatly increased
use of 1,2,5,6,9,10-hexabromocyclododecane (HBCDD, also known as HBCD)
as a flame retardant in consumer products. The physiochemical
similarities between HBCDD and PBDEs suggest that HBCDD may also be
neurotoxic to the dopamine system, which is specifically damaged in
Parkinson disease (PD). The purpose of this study was to assess the
neurotoxicity of HBCDD on the nigrostriatal dopamine system using an in
vitro and in vivo approach. We demonstrate that exposure to HBCDD
(0-25μM) for 24hrs causes significant cell death in the SK-N-SH
catecholaminergic cell line, as well as reductions in the growth and
viability of TH+ primary cultured neurons at lower concentrations
(0-10μM) after 72hrs of treatment. Assessment of the in vivo
neurotoxicity of HBCDD (25mg/kg for 30days) resulted in significant
reductions in the expression of the striatal dopamine transporter and
vesicular monoamine transporter 2, both of which are integral in
mediating dopamine homeostasis and neurotransmission in the dopamine
circuit. However, no changes were seen in the expression of tyrosine
hydroxylase in the dopamine terminal, or striatal levels of dopamine. To
date, these are the first data to demonstrate that exposure to HBCDD
disrupts the nigrostriatal dopamine system. Given these results and the
ubiquitous nature of HBCDD in the environment, its possible role as an
environmental risk factor for PD should be further investigated.

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