At the Society of Toxicology 58th Annual Meeting and ToxExpo from March 10th to 14th at the Baltimore Convention Center, poster presentation on Monday March 11th 10:45am – 12:15pm Poster Board P517 Convention Center Exhibition Hall sponsored by Professor Ruth Roberts.
Classification of Drug-Induced Seizure-Like Activities in Cultured Human iPSC-Derived Neurons.
Authors: Y. Ishibashi, A. Odawara, N. Matsuda, and I. Suzuki. Tohoku Institute of Technology, Sendai, Miyagi, Japan. Sponsor: R. Roberts
Human induced pluripotent stem cell-derived neurons are promising for use in toxicity evaluations in nonclinical studies. One of the major adverse events affecting the central nervous system observed during clinical trials is convulsions. Micro-electrode array (MEA) systems have recently attracted attention for use in evaluating the convulsion potential of a drug because they non-invasively measure the electrophysiological activity of neural networks at multiple sites in a high-throughput manner. MEA subteam of Neurotoxicity (NeuTox) Committee in Health and Environmental Science Institute (HESI) initiated the NeuTox Micro-Electrode Array (MEA) Subteam initiated pilot study using MEA for the prediction of seizure liability of drugs. Human iPSC-derived cortical neurons were cultured on 24-wells MEA plate for extracellular recording using Presto. Twelve compounds (pentylenetetrazole, picrotoxin, 4-aminopyrdine, linopyridine, amoxapine, strychnine, pilocarpine, amoxicillin, chlorpromazine, enoxacin, phenytoin and acetaminophen) were tested at 5 concentrations for each compound. Using spontaneous firings data to drug administration, we identified the parameter sets that can separate the responses between convulsive drugs and negative control, and the responses among the several convulsants with different action mechanism using principal component analysis and clustering methods. These analysis methods will be effective for detecting convulsive response and predicting mechanism of action of convulsive drugs.
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