Citation:

Shafer, Tim, C. Frank, J. Brown, AND K. Wallace. Using cortical cultures grown on microelectrode arrays to screen compounds for potential developmental neurotoxicity based on changes in network formation. 10th World Congress of Toxicology, Seattle, Washington, August 20 - 29, 2017.

Impact/Purpose:

Fewer than 1% of all environmental compounds have been tested for the potential to cause developmental neurotoxicity, thus, higher throughput testing approaches are needed to protect the health of developing individuals. The assay described in this abstract allows for testing of hundreds of compounds for their ability to disrupt developing neural networks and will be useful for screening compounds for potential developmental neurotoxicity.

Description:

Characterization of developmental neurotoxicity (DNT) hazard lags behind that of other adverse outcomes (e.g. hepatotoxicity) for thousands of compounds due the cost, time and number of animals needed to characterize DNT hazard. Thus, faster, less expensive approaches for DNT testing are needed. To address this, we have developed a microelectrode array (MEA)-based assay to screen for chemical effects on neural network formation. Primary cortical neurons grown on MEAs spontaneously form inter-connected networks, this allows spatial and temporal measurement of action potential spikes and bursts in these developing networks, and assessment of chemical effects on network formation. We screened a set of 60 compounds known to cause developmental neurotoxicity in vivo, 49 of which altered network development. By comparing the potency of effects on network function to cell viability, compounds can be prioritized for additional testing based on the specificity of effects on network formation. (This work was supported by the US Environmental Protection Agency. This abstract does not reflect EPA policy).

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