Neurotransmission on Fire?: Metabolic Activation Heightens Effect of PBDEs

Abstract

Vol. 116, No. 5 EnvironewsOpen AccessNeurotransmission on Fire?: Metabolic Activation Heightens Effect of PBDEs Julia R. Barrett Julia R. Barrett Search for more papers by this author Published:1 May 2008https://doi.org/10.1289/ehp.116-a214bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Polybrominated diphenyl ethers (PBDEs) are man-made flame retardants used in a variety of consumer products, including fabrics, cushion foam, carpet pads, computers, and electronic equipment. Ubiquitous in the environment, PBDEs and their metabolites are being found in wildlife and humans, but little is known about the human health effects of these chemicals. A new study now reveals that 6-OH-BDE-47, a hydroxylated metabolite of the widely used BDE-47, induces a more potent response than the parent compound in terms of intracellular calcium concentration (denoted [Ca2+]i) and release of catecholamine neurotransmitters [EHP 116:637–643; Dingemans et al.]. This finding suggests that metabolic activation could increase the neurotoxic potential of PBDEs.[Ca2+]i controls biological processes such as neurotransmitter release by fluctuating in response to chemical and electrical signals. In cell culture studies, high concentrations of PBDEs induced an increase in intracellular Ca2+. In vitro endocrine studies have further revealed that 6-OH-BDE-47 interacts more strongly with hormone receptor systems than its parent compound. Preliminary evidence suggests that exposure to high concentrations of PBDEs may cause neurobehavioral alterations and affect the immune system in animals. Exposure of newborn mice to high concentrations of BDE-47 alters behavior, learning and memory, and brain protein density and enzyme activity.The authors used cultured rat pheochromocytoma (PC12) cells, which secrete catecholamines upon stimulation, to compare the effects of 6-OH-BDE47 with those of BDE-47 on intracellular Ca2+ balance and catecholamine release. Members of the team had earlier measured the frequency of vesicular catecholamine release in individual cells in response to 6-OH-BDE-47 exposure and found that a high concentration of BDE-47 (20 μM) could trigger catecholamine release in PC12 cells. In the current study, they found that a lower concentration (5 μM) of 6-OH-BDE-47 caused an even stronger response. Moreover, 1 μM 6-OH-BDE-47 caused an initial transient increase in [Ca2+]i that was temporally related to catecholamine release. At 6-OH-BDE-47 concentrations of 1 μM or higher, they observed a delayed, dose-dependent increase in [Ca2+]i. Additional experiments revealed that the initial increase originated from emptying of the endoplasmic reticulum, whereas the delayed increase originated primarily from mitochondria.Based on these findings, the authors conclude that 6-OH-BDE-47 can disrupt intracellular Ca2+ levels and trigger neurotransmitter release at lower levels than its parent compound, BDE-47. This conclusion suggests the neurotoxic potential of PBDEs may be strongly enhanced by oxidative metabolism, which is especially relevant for children, who may be exposed to higher levels of PBDE than adults at a time when their brains are still developing. Given recent findings that hydroxylated PBDE metabolites, including 6-OH-BDE-47, bioaccumulate in the serum of children, further investigation of potential neurotoxicity is vital.FiguresReferencesRelatedDetails Vol. 116, No. 5 May 2008Metrics About Article Metrics Publication History Originally published1 May 2008Published in print1 May 2008 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.