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CHANGES IN PROTEOMIC PROFILES OF CEREBELLUM AND HIPPOCAMPUS FOLLOWING EXPOSURE TO A DEVELOPMENTAL NEUROTOXICANT.
Citation:
KODAVANTI, PRASADA RAO S., J. E. ROYLAND, T. V. RAMABHADRAN, AND O. ALZATE. CHANGES IN PROTEOMIC PROFILES OF CEREBELLUM AND HIPPOCAMPUS FOLLOWING EXPOSURE TO A DEVELOPMENTAL NEUROTOXICANT. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
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 adversely affect human health, including learning and memory. Although the cellular and molecular basis is still unclear, a series of in vitro and in vivo studies have revealed that in addition to the effects on thyroid hormones, the disruption of Ca2+ homeostasis and Ca2+-mediated signal transduction play significant roles in PCB-induced developmental neurotoxicity. The culminating event in a variety of signal transduction pathways is the regulation of gene and protein expression, which ultimately has an effect on the growth and function of the nervous system. Our previous results showed changes in gene expression profiles related to signal transduction and neuronal growth. In this study, the protein expression profiles in cerebellum and hippocampus following PCB developmental exposure were examined. 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, and the cerebellum and the hippocampus from PND14 animals were analyzed. Proteins differentially expressed following chemical exposure were isolated by two-dimensional differential gel electrophoresis using fluorescent cyanine dyes and identified by mass spectrometry (MS). Two proteins were found to be differentially expressed in the cerebellum following chemical exposure while 18 proteins were differentially expressed in the hippocampus. MS identification revealed that these proteins are related to energy metabolism in mitochondria (creatine kinase and malate dehydrogenase), calcium signaling (endoplasmic reticulum ATPase and Ryanodine receptor type II) or growth of the nervous system (collapsing response mediator protein 3 (CRMP-3)). These results suggest that changes in energy metabolism and intracellular signaling may be involved in the developmental neurotoxicity of persistent chemicals. (This abstract does not necessarily reflect USEPA policy).