Ontogenetic alterations in prototypical transcription factors in the rat cerebellum and hippocampus following perinatal exposure to a commercial PCB mixture.
Polychlorinated biphenyls (PCBs) are prevalent in the environment despite the ban of their use for decades and offer a model system to understand developmental neurotoxicity of persistent pollutants. Disturbances in brain development and cognition are among the neurotoxic manifestations of PCBs. The cellular and molecular basis for PCB-induced developmental neurotoxicity is still unclear; however, a series of in vitro and some in vivo studies have revealed that the disruption of Ca(2+) homeostasis and Ca(2+)-mediated signal transduction play a significant role. The culminating event in a variety of signal transduction pathways is the regulation of gene expression. Therefore, we examined the DNA-binding of prototypical transcription factors in order to identify those that are involved in signal transduction-transcription coupling in the cerebellum and hippocampus of developing rat brains following exposure to a commercial PCB mixture Aroclor 1254. Pregnant rats (Long Evans) were exposed perinatally to 0 or 6 mg/kg/day of Aroclor 1254 (Accu Standard Inc., Lot # 124-191) from gestational day 6 through postnatal day (PND) 21. On specific time points such as days 7, 14, 21, and 60, the DNA-binding of various transcription factors (Sp1, AP-1, NF-kappaB and CREB) was monitored in the cerebellum and hippocampus by a gel mobility shift assay. The induction of DNA-binding of transcription factors was more pronounced during the first 2 weeks after birth than at later periods. Sp1, AP1, and NF-kappaB exhibited a significant increase in DNA-binding following PCB exposure and peaked between 7 and 14 days after birth. However, the DNA-binding activity of CREB remained unchanged. These distinct changes delineate the involvement of specific transduction-transcription coupling pathways that may mediate PCB-induced perturbations in developmental gene expression.
Basha
Md Riyaz
MR
Department of Biomedical Sciences and Pharmaceutical, University of Rhode Island, RI 02881, USA.
Braddy
Nykeba S
NS
Zawia
Nasser H
NH
Kodavanti
Prasada Rao S
PR
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D020111:Chlorodiphenyl (54% Chlorine) / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D020111:Chlorodiphenyl (54% Chlorine)