Medicine and Health Sciences Commons^™

Transcriptional Profiles For Glutamate Transporters Reveal Differences Between Organophosphates But Similarities With Unrelated Neurotoxicants, Theodore A. Slotkin, Doug Lobner, Frederic J. Seidler

Biomedical Sciences Faculty Research and Publications

The developmental neurotoxicity of organophosphates involves mechanisms other than their shared property as cholinesterase inhibitors, among which are excitotoxicity and oxidative stress. We used PC12 cells as a neurodevelopmental model to compare the effects of chlorpyrifos and diazinon on the expression of genes encoding glutamate transporters. Chlorpyrifos had a greater effect in cells undergoing nerve growth factor-induced neurodifferentiation as compared to undifferentiated PC12 cells, with peak sensitivity at the initiation of differentiation, reflecting a global upregulation of all the glutamate transporter genes expressed in this cell line. In differentiating cells, chlorpyrifos had a significantly greater effect than did diazinon and …