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A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYS
Citation:
Strickland, J., K. Wallace, P. Valdivia, W. Mundy, AND Tim Shafer. A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYS. Soxciety of Toxicology Meeting, San Diego, CA, March 22 - 27, 2015.
Impact/Purpose:
To be presented at the annual SOT meeting 2015
Description:
AbstractTITLE: A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYSABSTRACT BODY: Microelectrode array (MEA) recordings are increasingly being used as an in vitro method to detect and characterize the ability of drugs, chemicals and particles to cause neurotoxicity. While effects of compounds on spontaneous network activity in MEAs is easily measured by MEA recordings, compound cytotoxicity is not routinely determined, particularly within the same well from which recordings are collected. In the present experiments, primary cultures from rat cortex were exposed to six compounds (glyphosate, beta-cyfluthrin, domoic acid, tributyltin, lindane and fipronil) in multi-well MEA (mwMEA; 48 well) plates. Effects of these compounds (0.03-100 µM) on spontaneous network activity (mean firing rate; MFR) and release of cytotoxicity marker lactate dehydrogenase (LDH) were determined following 60 min exposure. Glyphosate did not effect MFR or LDH release. By contrast, tributyltin decreased MFR coincident with increased LDH release. Domoic acid and beta-cyfluthrin decreased MFR in a concentration-dependent manner without altering LDH release. Lindane and fipronil also did not alter LDH release, but caused biphasic alterations in MFR, with increases in MFR at lower followed by decreases at higher concentrations. These results demonstrate a simple and rapid method for within well determination of compound effects on network function and viability in mwMEA plates. This multiplexed assay will facilitate neurotoxicity screening. (This abstract does not reflect Agency policy)