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Evaluation of a Microelectrode Arrays for Neurotoxicity Testing Using a Chemical Training Set
Citation:
McConnell, E. R., M. McClain, J. Ross, W. LaFew, AND T. J. SHAFER. Evaluation of a Microelectrode Arrays for Neurotoxicity Testing Using a Chemical Training Set. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
Microelectrode array (MEA) approaches have been proposed as a tool for detecting functional changes in electrically active cells, including neurons, exposed to drugs, chemicals, -or particles. However, conventional single well MEA systems lack the throughput necessary for screening large numbers of chemicals
Description:
Microelectrode array (MEA) approaches have been proposed as a tool for detecting functional changes in electrically active cells, including neurons, exposed to drugs, chemicals, or particles. However, conventional single well MEA systems lack the throughput necessary for screening large numbers of chemicals. The current experiments used primary cortical neurons grown on Multi-well MEA (MW MEA) plates to screen a training set of 30 chemicals. Each MEA plate contained 12 wells with 64 microelectrodes/well, for a total of 768 channels. Of the 30 chemicals evaluated, 23 were known to alter neuronal function ("positives"), including 6 GABAergic and 3 glutamatergic compounds, 4 pyrethroids, 3 metals. 2 cholinesterase inhibitors, 2 nicotinic acetylcholine receptor agonists, valproic acid, verapamil, and fluoxetine. Seven compounds (glyphosate, acetaminophen, dimethyl phthalate, paraquat, saccharin, d-sorbitol, amoxicillin), expected to have no effect on neuronal function, were tested as "negatives." Chemical effects (50 uM or highest soluble concentration) were assessed for 30 min between 14 and 22 DIV, following collection of 30 min baseline activity. Twenty of the positives altered either the mean network spike rate, number of active electrodes or both by more than the DMSO control. The three positives without effect were valproic acid, nicotine and imidacloprid. None of the negative compounds changed activity by more than DMSO. Based on these results, the MW MEA assay has both high sensitivity and specificity, indicating that cortical neurons grown on MW MEAs are a useful approach to screen chemicals for neurotoxic effects mediated by a broad variety of mechanisms. (This abstract does not reflect Agency Policy).