title: A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity.
abstract: Polybrominated diphenyl ethers (PBDEs), extensively used in the past few decades as flame retardants in a variety of consumer products, have become world-wide persistent environmental pollutants. Levels in North America are usually higher than those in Europe and Asia, and body burden is 3-to-9-fold higher in infants and toddlers than in adults. The latter has raised concern for potential developmental toxicity and neurotoxicity of PBDEs. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or post-natal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly in the domains of motor activity and cognition. The mechanisms underlying the developmental neurotoxic effects of PBDEs are not known, though several hypotheses have been put forward. One general mode of action relates to the ability of PBDEs to impair thyroid hormone homeostasis, thus indirectly affecting the developing brain. An alternative or additional mode of action involves a direct effect of PBDEs on nervous system cells; PBDEs can cause oxidative stress-related damage (DNA damage, mitochondrial dysfunction, apoptosis), and interfere with signal transduction (particularly calcium signaling), and with neurotransmitter systems. Important issues such as bioavailability and metabolism of PBDEs, extrapolation of results to low level of exposures, and the potential effects of interactions among PBDE congeners and between PBDEs and other contaminants also need to be taken into account.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Department of Neuroscience, University of Parma, Parma, Italy. Electronic address: lgcosta@u.washington.edu.
authors.forename: Lucio G
authors.initials: LG
authors.lastname: Costa
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Rian
authors.initials: R
authors.lastname: de Laat
authors.affiliation: Department of Neuroscience, University of Parma, Parma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tagliaferri
authors.affiliation: Department of Neuroscience, University of Parma, Parma, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pellacani
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D055768:Halogenated Diphenyl Ethers; D013963:Thyroid Hormones; D005978:Glutathione
keywords: Apoptosis; Calcium signaling; Developmental neurotoxicity; Oxidative stress; Polybrominated diphenyl ethers; Thyroid hormone homeostasis