Real-Time Monitoring of Levetiracetam Effect on the Electrophysiology of an Heterogenous Human iPSC-Derived Neuronal Cell Culture Using Microelectrode Array Technology

Biosensors (Basel). 2021 Nov 12;11(11):450. doi: 10.3390/bios11110450.

Abstract

Levetiracetam (LEV) is a broad-spectrum and widely used antiepileptic drug that also has neuroprotective effects in different neurological conditions. Given its complex interaction with neuronal physiology, a better comprehension of LEV effects on neurons activity is needed. Microelectrode arrays (MEAs) represent an advanced technology for the non-invasive study of electrophysiological activity of neuronal cell cultures. In this study, we exploited the Maestro Edge MEA system, a platform that allows a deep analysis of the electrical network behavior, to study the electrophysiological effect of LEV on a mixed population of human neurons (glutamatergic, GABAergic and dopaminergic neurons, and astrocytes). We found that LEV significantly affected different variables such as spiking, single-electrode bursting, and network bursting activity, with a pronounced effect after 15 min. Moreover, neuronal cell culture completely rescued its baseline activity after 24 h without LEV. In summary, MEA technology confirmed its high sensitivity in detecting drug-induced electrophysiological modifications. Moreover, our results allow one to extend the knowledge on the electrophysiological effects of LEV on the complex neuronal population that resembles the human cortex.

Keywords: Levetiracetam; biosensors; drug screening; electrophysiology; iPSC-derived neurons; microelectrode array; real-time monitoring.

MeSH terms

  • Cell Culture Techniques
  • Electrophysiological Phenomena
  • Humans
  • Induced Pluripotent Stem Cells* / drug effects
  • Levetiracetam* / pharmacology
  • Microelectrodes*
  • Neurons* / drug effects

Substances

  • Levetiracetam