Integrated Omic Analyses Identify Pathways and Transcriptomic Regulators Associated with Chemical Alterations of in Vitro Neural Network Formation

Authors: Marable CA, Frank CL, Seim RF, Hester S, Henderson WM, Chorley B, and Shafer TJ.

Toxicological Sciences, 2021.

Axion’s bioelectronic assays may provide a faster, cheaper, more humane developmental neurotoxicity platform for studying links between hazardous chemicals and disease

Direct or in utero exposure to certain chemicals in use today has been linked to developmental disorders and neurological diseases, but thousands of compounds remain insufficiently tested and current risk assessment strategies are limited in their ability to predict or explain adverse effects in humans. Furthermore, current testing methods are costly, time-consuming, and often rely on a large number of animals. To address these shortcomings, scientists propose that novel screening approaches are essential for better understanding the transcriptomic and metabolomic impact of hazardous chemicals on complex developing neural networks.

In this study, researchers used Axion’s Maestro microelectrode array (MEA) platform to noninvasively examine the electrophysiological effects of six known neurotoxicants on rat primary cortical neurons in vitro over 12 days. At the end of the exposure, the team conducted transcriptomic and metabolomic analyses of media and cell lysates to explore possible pathways, biomarkers, and genes associated with abnormal neural network development.

The overall findings of the combined -omic analysis showed that exposure to different classes of compounds produced different effects on developing neural networks in vitro and revealed that alterations in network formation were accompanied by transcriptomic and metabolomic changes—results that demonstrate the feasibility of the in vitro approach for testing potential neurotoxicants and suggest pathways underlying observed functional changes. Looking forward, this faster, cheaper, more humane developmental neurotoxicity platform may enable scientists to better understand links between chemicals and neurological diseases and disorders in the future.