title: Perinatal exposure to BDE-99 causes learning disorders and decreases serum thyroid hormone levels and BDNF gene expression in hippocampus in rat offspring.
abstract: Exposure of pregnant women to polybrominated diphenyl ethers (PBDEs) may mean serious health risks. The main goal of the present study was to examine the neurobehavioral changes in rat offspring that were perinatally exposed to one of the most prevalent PBDEs congeners found in humans, 2,2',4,4',5-pentaBDE (BDE-99). Rat dams were exposed to 0, 1 and 2mg/kg/day of BDE-99 from gestation day 6 to post-natal day 21. When pups were weaning, cortex and hippocampal gene expressions of brain-derived neurotrophic factor (BDNF) of the different isoforms of the thyroid hormone (TH) receptors (TRs) were evaluated. Serum TH levels were also determined. The remaining pups were assessed by neurobehavioral testing for learning and memory function. The results showed that maternal transference of BDE-99 produced a delay in the spatial learning task in the water maze test. Moreover, the open-field test revealed a significant dose-response anxiolytic effect. It was also found that the serum levels of triiodothyronine (T3), tetraiiodothyronine (T4) and free-T4 (FT4) decreased. Although no effect on the gene expression of the different isoforms of TRs was observed, the expression of the TH-mediated gene BDNF was down-regulated in the hippocampus. These results indicate a clear signal disruption of TH and reinforce previous studies in which neurotoxic effects of PBDEs in animal research were observed at levels comparable to those found in humans.
authors.affiliation: Laboratory of Toxicology and Envirsonmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201 Reus, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Blanco
authors.forename: Miquel
authors.initials: M
authors.lastname: Mulero
authors.forename: Luis
authors.initials: L
authors.lastname: Heredia
authors.forename: Andreu
authors.initials: A
authors.lastname: Pujol
authors.forename: José L
authors.initials: JL
authors.lastname: Domingo
authors.forename: Domènec J
authors.initials: DJ
authors.lastname: Sánchez
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007859:Learning Disabilities / Q000097:blood* / Q000139:chemically induced; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D019208:Brain-Derived Neurotrophic Factor; D055768:Halogenated Diphenyl Ethers; D013963:Thyroid Hormones