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A Multiplexed Assay for Determination of Neurotoxicant Effects on Spontaneous Network Activity and Viability from Microelectrode Arrays.
Wallace, K., J. Strickland, P. Valdivia, W. Mundy, AND Tim Shafer. A Multiplexed Assay for Determination of Neurotoxicant Effects on Spontaneous Network Activity and Viability from Microelectrode Arrays. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, Netherlands, 49:79-85, (2015).
To be submitted to Neurotoxicology
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 is easily determined by MEA recordings, compound cytotoxicity is not routinely assessed, particularly within the same network from which recordings are collected. The present experiments sought to develop a multiplexed approach that allowed measurement of network activity and cell health in the same MEA well. Primary cultures from rat cortex were exposed to six different compounds (glyphosate, β-cyfluthrin, domoic acid, tributyltin, lindane and fipronil). Effects of these compounds (0.03-100 µM) on spontaneous network activity (mean firing rate; MFR), cellular metabolic activity (Alamar BlueTM (AB) assay) and lactate dehydrogenase (LDH) release were determined following a 60-min exposure. Glyphosate elicited no effect on MFR, LDH release or AB reduction. Tributyltin caused concomitant decreases in MFR and AB reduction and increases LDH release, while domoic acid and β-cyfluthrin decreased MFR in a concentration-dependent manner without altering either LDH release or AB reduction. By contrast, lindane and fipronil did not alter LDH release or AB reduction, but caused biphasic alterations in MFR, with increases in MFR at lower concentrations followed by decreases at higher concentrations. These results demonstrate a simple and rapid method for the simultaneous determination of test compound effects on spontaneous electrical activity and cell health from the same network, and will facilitate rapid screening of compounds for potential neurotoxicity.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION