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CHANGES IN GENE EXPRESSION PROFILE IN THE CEREBELLUM AND THE HIPPOCAMPUS FOLLOWING DEVELOPMENTAL EXPOSURE TO A NEUROTOXICANT.
Citation:
Kodavanti, PRS, T. R. Ward, AND J E. Royland. CHANGES IN GENE EXPRESSION PROFILE IN THE CEREBELLUM AND THE HIPPOCAMPUS FOLLOWING DEVELOPMENTAL EXPOSURE TO A NEUROTOXICANT. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
The vast literature on the group of chemicals known as polychlorinated biphenyls (PCBs) makes it a unique model to understand major issues related to environmental mixtures of persistent chemicals. At background levels of exposure, PCBs have been shown to affect human health including learning and memory dysfunction. Although the cellular and molecular basis for PCB-induced developmental neurotoxicity is still unclear, a series of in vitro and 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, which ultimately has an effect on the growth and function of the nervous system. Therefore, we examined the gene expression profile in cerebellum and hippocampus coupled with toxicity pathways following PCB developmental exposure. Pregnant rats (Long Evans) were dosed perinatally with 0 or 6 mg/kg/day of Aroclor 1254 (AccuStandard Inc., Lot # 124-191) from gestation day 6 through postnatal day (PND) 21. For the present study, only the cerebellum and the hippocampus from PNDs 7 and 14 animals were analyzed. RNA was extracted for analysis on Affymetrix mouse genome 430 2.0 chips. Preliminary analysis of the data indicated that expression levels of ~1600 genes in the cerebellum and ~ 1200 genes in the hippocampus were changed by >1.5 fold from PND7 to 14. Of those genes, 370 were common in these two brain regions. Following exposure to Aroclor 1254, the number of genes affected > 1.5 fold were greater at PND 7 (~150 genes) compared to PND 14 (~ 100 genes) in hippocampus and cerebellum. The greatest proportions of genes altered were related to signal transduction, cell communication, and transcription factors. These results suggest that changes in intracellular signaling and related gene expression may be involved in mediating PCB-induced neurotoxic effects. (The abstract does not necessarily reflect USEPA policy).