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Multi-well microelectrode array recordings detect neuroactivity of ToxCast compounds.

Pablo Valdivia1, Matt Martin2, William R LeFew3

  • 1Axion Biosystems, Atlanta, GA, United States.

Neurotoxicology
|July 6, 2014
PubMed
Summary
This summary is machine-generated.

Multi-well microelectrode arrays (MEAs) efficiently screen chemical neurotoxicity. This method aligns with ion channel assay predictions but shows limitations with nicotinic compounds.

Keywords:
ElectrophysiologyMicroelectrode arraysScreeningToxCast

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Area of Science:

  • Neuroscience
  • Toxicology
  • Assay Development

Background:

  • Spontaneous neuronal activity in cultures is sensitive to chemical and drug effects.
  • Multi-well microelectrode array (mwMEA) systems enhance throughput for chemical screening.
  • The US Environmental Protection Agency's (EPA) ToxCast program utilizes high-throughput screening assays.

Purpose of the Study:

  • To evaluate the utility of mwMEAs for screening EPA ToxCast compounds for neurotoxic effects.
  • To assess the concordance between mwMEA results and ToxCast Novascreen ion channel (NVS_IC) assay predictions.
  • To identify potential neurotoxicants and understand discrepancies between screening platforms.

Main Methods:

  • Primary cortical neurons in 48-well MEA plates were exposed to ToxCast compounds.
  • Baseline neuronal activity was recorded before compound exposure.
  • Weighted mean firing rate (wMFR) was analyzed to identify compounds altering neuronal activity beyond a defined threshold.

Main Results:

  • 54 out of 68 compounds in the first cohort and 13 out of 25 in the second cohort altered wMFR.
  • MEAs detected 81.1% of compounds positive in NVS_IC assays.
  • MEAs identified neurotoxicants not detected by NVS_IC assays, such as pyrethroids and GABAA antagonists, but showed insensitivity to most nicotinic compounds.

Conclusions:

  • mwMEAs provide an efficient platform for screening chemical neurotoxicity.
  • Results show good concordance with NVS_IC assays for ion channel interactions.
  • MEAs offer complementary neurotoxicity detection, particularly for compounds affecting neuronal network activity differently than ion channel binding alone.