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Toxic insult by PCBs results in learning and memory deficits in humans. Alterations in expression of neurotrophic factors and/or their receptors have been linked to changes in cognition. How PCBs affect cognition is not known. We propose that PCBs affect cognition by altering neurotrophic factor expression or effects. We exposed cultured C6 glial cells in medium containing PCB (Aroclor 1254 (10ppm)). Control cells were treated with DMSO or regular medium. Cells were incubated at 37o C for up to 72 hours. Medium samples were taken at 6hr, 24hr, 48hr, and 72hr intervals. Enzyme-linked immunosorbent assays (ELISA) were used to determine both glial cell-line derived neurotrophic growth factor (GDNF) and nerve growth factor (NGF) concentrations in all samples. In addition, we removed the brain from rats exposed to10ppm, 50ppm, and 0ppm PCB in their diet for 7 or 84 days. One cerebral hemisphere from each animal was homogenized and analysized by ELISA for GDNF and NGF content. PCB increased GDNF but not NGF expression in Glial cells. Contrary to our in-vitro data, PCB treated rats had significantly reduced GDNF and NGF in their brains. Our data show that exposure of neural tissues to PCBs, alters NGF and GDNF expressions and hence offers a basis whereby PCB may alter neural plasticity.