Perinatal exposure to BDE-99 causes learning disorders and decreases serum thyroid hormone levels and BDNF gene expression in hippocampus in rat offspring

被引:39
作者
Blanco, Jordi [1 ,2 ]
Mulero, Miquel [3 ]
Heredia, Luis [1 ,4 ]
Pujol, Andreu [2 ]
Domingo, Jose L. [1 ]
Sanchez, Domenec J. [1 ,2 ]
机构
[1] Univ Rovira & Virgili, IISPV, Sch Med, Lab Toxicol & Environm Hlth, Reus 43201, Spain
[2] Univ Rovira & Virgili, IISPV, Sch Med, Physiol Unit, E-43201 Reus, Spain
[3] Univ Rovira & Virgili, Dept Biochem & Biotechnol, Nutrigenom Grp, E-43007 Tarragona, Spain
[4] Univ Rovira & Virgili, Dept Psychol, CRAMC, E-43007 Tarragona, Spain
关键词
Polybrominated diphenyl ethers (PBDEs); 2,2 ',4,4 ',5-pentaBDE (BDE-99); Brain derived neurotrophic factor (BDNF); Thyroid receptors (TRs); Thyroid hormones (THs); POLYBROMINATED DIPHENYL ETHERS; BROMINATED FLAME RETARDANTS; LONG-TERM POTENTIATION; LOW-DOSE PBDE-99; DEVELOPMENTAL EXPOSURE; NEONATAL EXPOSURE; BREAST-MILK; 2,2',4,4',5-PENTABROMODIPHENYL ETHER; LACTATIONAL EXPOSURE; SPONTANEOUS BEHAVIOR;
D O I
10.1016/j.tox.2013.03.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 2 mg/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 downregulated 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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:122 / 128
页数:7
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