Detection of polybrominated diphenyl ethers in herring gull (Larus argentatus) brains: effects on mRNA expression in cultured neuronal cells.
In recent years, polybrominated diphenyl ethers (PBDEs) have been detected at increasing levels in the environment due to their widespread use as flame retardants. PBDEs can affect thyroid hormone homeostasis and the cholinergic neurotransmitter system. In this study, several PBDE congeners were detected in whole brain samples and neuronal cells of herring gulls (Larus argentatus). A herring gull neuronal cell culture method was used to determine the effects of PBDEs on cytotoxicity and mRNA expression. Real-time RT-PCR assays were developed for genes associated with the thyroid hormone pathway (thyroid hormone receptors [TR alpha and beta], transthyretin [TTR]), and the cholinergic system (neuronal nicotinic acetylcholine receptor alpha-7 [nAChR alpha-7]). Administration of T3 resulted in a significant up-regulation of the two TRs and a significant down-regulation of TTR. TTR was also down-regulated by the commercial penta-BDE mixture, DE-71. In contrast, neither DE-71, nor BDE-47, -99, or -100 altered the mRNA levels of the TRs or nAChR alpha-7. The in vitro approach was a relevant model system for assessing the effects of PBDEs on cytotoxicity and mRNA expression. Herring gull neuronal cells were responsive to both T3 and PBDEs although, receptors associated with two predicted mechanisms of PBDE action were not effective molecular biomarkers of exposure.
Crump
Doug
D
Environment Canada, National Wildlife Research Centre, Ottawa, Ontario, Canada. doug.crump@ec.gc.ca
Jagla
Magdalena M
MM
Kehoe
Amy
A
Kennedy
Sean W
SW
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D046091:Charadriiformes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010647:Phenyl Ethers / Q000032:analysis*; D011075:Polybrominated Biphenyls / Q000032:analysis*; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D011228:Prealbumin; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D011988:Receptors, Thyroid Hormone; D064569:alpha7 Nicotinic Acetylcholine Receptor; D014284:Triiodothyronine