Toxicity of organophosphate and carbamate pesticides for neuronal and non-neuronal cells

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Project Period: 
2014
Project Investigator(s): 
J. Doorn, Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa
Abstract: 

Organophosphate (OP) and carbamate pesticides are widely used in agriculture. Acute exposure to high doses may cause cholinergic toxicity; however, recent work demonstrates that exposure to low levels causes adverse effects in humans from neurological deficits to oxidative stress/reactive oxygen species (ROS). The mechanism for this “non-canonical” toxicity is unknown but concerning given the ubiquitous nature of OP and carbamates in the environment and significant human exposure. Such adverse consequences are likely due to effects of these pesticides on cell types found in the brain other than cholinergic neurons, such as other neurons or glial cells (non-neuronal). The goal of this project is to determine which neuron types (i.e., cholinergic, glutamatergic, dopaminergic) or non-neuronal cells (i.e., astrocyte) are most sensitive to OP and carbamate pesticides, yielding toxicity and/or oxidative stress/ROS. In addition, the investigator seeks to identify the insulting species of the OP agent, i.e., phosphorothioate or bioactive oxon metabolite.