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CHANGES IN NUCLEAR TRANSCRIPTION FACTORS IN RAT HIPPOCAMPUS AND CEREBELLUM FOLLOWING DEVELOPMENTAL EXPOSURE TO A COMMERCIAL PCB MIXTURE.
Citation:
Basha, M. R., N. H. Zawia, AND PRS Kodavanti. CHANGES IN NUCLEAR TRANSCRIPTION FACTORS IN RAT HIPPOCAMPUS AND CEREBELLUM FOLLOWING DEVELOPMENTAL EXPOSURE TO A COMMERCIAL PCB MIXTURE. Presented at 21st International Neurotoxicology Conference, Honolulu, Hawaii, February 10-14, 2004.
Description:
Polychlorinated biphenyls (PCBs) offer a unique model to understand the major issues related to complex environmental mixtures. These pollutants are ubiquitous and exist as mixtures of several congeners in the environment. Human exposures to PCBs are associated with a variety of adverse health effects including neurobehavioral changes and neuroendocrine disruption. It is of a particular concern that exposure to relatively low levels during development may be associated with neurological deficits such as impairments in learning and memory. During the past decades there has been an attempt to understand the cellular and molecular basis of PCB-induced neurotoxic effects in animal models. It has been proposed that the disruption of Ca2+ homeostasis and Ca2+ mediated signal transduction may be involved in mediating the effects of PCBs. These changes in second messenger systems may be coupled to gene expression. We have examined the DNA-binding of some of the transcription factors in order to identify those that are involved in signal transduction/transcription coupling in the developing cerebella and hippocampi of PCB-exposed animals. 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 PNDs viz., 7, 14, 21, and 60, the cerebellum and the hippocampus were isolated. The DNA-binding of transcription factors such as specificity protein (Sp1), activator protein (AP1), nuclear factor kappaB (NF-kB), and cAMP responsive element modulator (CREB) were evaluated using gel mobility shift assays. Developmental exposure to PCBs resulted in an increase in the DNA-binding of Ap1, Sp1 and NF-kB in the hippocampus and the cerebellum until the third week after birth; however, the induction was more pronounced on PND 14. CREB in the hippocampus was increased significantly on PND14. These distinct changes in nuclear transcription factors suggest that exposure to PCBs may lead to perturbations in gene expression in the developing brain. (This abstract does not necessarily reflect USEPA policy).