Alterations in gene expression of glutamate receptors and exocytosis-related factors by a hydroxylated-polychlorinated biphenyl in the developing rat brain.
Polychlorinated biphenyls (PCBs), major environmental hormonally active agents, are metabolized into hydroxylated PCBs in the liver to facilitate excretion. Some of hydroxylated PCBs also have potencies disturbing endogenous hormonal activities at least in vitro. Hormonal activities of hydroxylated PCBs raise a possibility of their interfering with normal brain development which is strictly regulated by endogenous hormones. We investigated whether and how prenatal exposure to a congener of hydroxylated PCBs (4-OH-2',3,3',4',5'-penta CB; 4-OH-PCB106) having activities to disrupt thyroid hormone-dependent signals in vitro could perturb normal gene expression in the developing brain in vivo. Pregnant rats were exposed to 4-OH-PCB106 subcutaneously at the dose of 1.0mg/(kgday) from day 7 of gestation to postnatal day 1. Then three brain regions (cerebral cortex, hippocampus and striatum) were obtained from offspring on postnatal day 1 and subjected to further gene expression analyses. Comprehensive analyses of mRNA expression by oligo DNA microarrays and subsequent validations by quantitative RT-PCR revealed that prenatal exposure to 4-OH-PCB106 affected mRNA expression of glutamate receptors as well as that of thyroid hormone-responsive genes in region-specific manners. Concomitantly 4-OH-PCB106 exposure increased mRNA expression of genes related to exocytosis in the three brain regions. These results raise the possibility that prenatal exposure to some hydroxylated PCBs with thyroid hormone-disrupting potencies leads to abnormal brain development via perturbations on the expression of genes involved in glutamatergic neurotransmission.
Takahashi
Masaki
M
Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University, 5-10-1 Fuchinobe, Sagamihara, Kanagawa 229-8558, Japan.
Negishi
Takayuki
T
Imamura
Makoto
M
Sawano
Erika
E
Kuroda
Yoichiro
Y
Yoshikawa
Yasuhiro
Y
Tashiro
Tomoko
T
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000196:embryology; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D005089:Exocytosis / Q000187:drug effects* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology; D006900:Hydroxylation; D015918:Infusion Pumps, Implantable; D020411:Oligonucleotide Array Sequence Analysis; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics
D052244:Endocrine Disruptors; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D011988:Receptors, Thyroid Hormone; D011078:Polychlorinated Biphenyls