title: Thyroid hormone disruption and cognitive impairment in rats exposed to PBDE during postnatal development.
abstract: Polybrominated diphenyl ether flame-retardants (PBDEs) are thyroid-disrupting environmental chemicals. We investigated the effects of postnatal exposure to DE-71 (a mixture of tetra- and penta-brominated congeners), n-propylthiouracil (PTU) and thyroxine (T4) replacement on open-field (OF) and radial maze (RAM) tests. Wistar rats (5 males/5 females per litter, 32 litters) were treated orally (PND 5-22) with PTU (4mg/kg bw/d), DE-71 (30mg/kg bw/d), with and without co-administration of T4 (15μg/kg bw/d, sc). PTU depressed T4 serum levels and body weight gain and enlarged thyroid gland. Although decreasing T4 levels, DE-71 did not change thyroid and body weights. PTU-treated rats showed hyperactivity (PND 42 and 70), and working and reference memory learning deficits (RAM, PND 100). Although not altering motor activity and working memory, DE-71 caused a reference memory deficit (females only). T4 co-administration averted hypothyroxinemia and long-term cognitive deficits caused by PTU and DE-71.
authors.affiliation: Laboratory of Environmental Toxicology, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil.
authors.forename: Andressa S
authors.initials: AS
authors.lastname: de-Miranda
authors.affiliation: Laboratory of Environmental Toxicology, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil.
authors.forename: Sergio N
authors.initials: SN
authors.lastname: Kuriyama
authors.affiliation: Laboratory of Environmental Toxicology, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil.
authors.forename: Camille S
authors.initials: CS
authors.lastname: da-Silva
authors.affiliation: Laboratory of Environmental Toxicology, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil.
authors.forename: Monicke S C
authors.initials: MS
authors.lastname: do-Nascimento
authors.affiliation: Laboratory of Environmental Toxicology, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil.
authors.forename: Thiago E M
authors.initials: TE
authors.lastname: Parente
authors.affiliation: Laboratory of Environmental Toxicology, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil. Electronic address: paum@ensp.fiocruz.br.
authors.forename: Francisco J R
authors.initials: FJ
authors.lastname: Paumgartten
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D060825:Cognitive Dysfunction / Q000139:chemically induced; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D014453:Glucuronosyltransferase / Q000235:genetics; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D017208:Rats, Wistar; D013974:Thyroxine / Q000097:blood*; D000099148:UGT1A1 Enzyme
chemical_list: D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D004785:Environmental Pollutants; D005411:Flame Retardants; D014453:Glucuronosyltransferase; D055768:Halogenated Diphenyl Ethers; D013974:Thyroxine; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme
keywords: Behavior; DE-71; Developmental neurotoxicity; Flame retardants; Learning; Liver enzyme induction; PBDEs; Polybrominated diphenyl ether; Thyroid function