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ONTOGENETIC ALTERATIONS IN PROTOTYPICAL FACTORS IN THE CEREBELLUM AND HIPPOCAMPUS FOLLOWING PERINATAL EXPOSURE TO A COMMERCIAL PCB MIXTURE.
Citation:
BASHA, R., N. S. BRADDY, N. H. ZAWIA, AND PRASADA RAO S. KODAVANTI. ONTOGENETIC ALTERATIONS IN PROTOTYPICAL FACTORS IN THE CEREBELLUM AND HIPPOCAMPUS FOLLOWING PERINATAL EXPOSURE TO A COMMERCIAL PCB MIXTURE. NEUROTOXICOLOGY. Intox Press, Inc, Little Rock, AR, 27:118-124, (2006).
Impact/Purpose:
To delineate the involvement of specific transduction-transcription coupling pathways that mediate PCB-induced perturbations in developmental gene expression
Description:
Polychlorinated biphenyls (PCBs) are prevalent in the environment despite the ban of their use for decades and offers as a model 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 Ca2+ homeostasis and Ca2+ 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 gestation day 6 through postnatal day (PND) 21. On specific time points such as day 7, 14, 21, and 60, the DNA-binding of various transcription factors: Sp1, AP-1, NF-:B and CREB were monitored in the cerebellum and hippocampus using gel mobility shift assays. The induction of DNA-binding of transcription factors was more pronounced during the first two weeks after birth. Sp1, AP1, and NF-:B exhibited a significant increase in DNA-binding following PCB exposure and peaked between 7-14 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 mediate PCB-induced perturbations in developmental gene expression.