It is time for the 9th edition of our monthly blog. Earlier this year, we have highlighted each month five papers dealing wiht a variety of scientific applications –Beta CellsBurst DetectionAxonsRetinaOrganoids and Human iPSC-Derived Neurons – as well as with a topic closely related to our daily operations, Spike Sorting. During the COVID-19 lockdown in April we published a special edition about Neurons and Viruses.

In our September edition we highlight the use of Microelectrode array (MEA) technology for drug screening. MEAs are used to evaluate the effect of drugs on neuronal physiological activity and the technology can be used to test the efficacy of compounds on impaired functional phenotype modeling neurological disorders (e.g. epilepsy). Furthermore, MEAs are used to evaluate the toxicity of compounds in neuronal cells. Therefore, for this Monthly Must-Reads edition, we decided to highlight the article written by Tukker AM et al., in which MEA technology was used for in vitro seizure liability assessment in three different commercially human iPSC-derived neuronal lines.

Towards Animal-Free Neurotoxicity Screening: Applicability of hiPSC-Derived Neuronal Models for In Vitro Seizure Liability Assessment.
by Anke M. Tukker, Regina G. D. M. van Kleef, Fiona M. J. Wijnolts, Aart de Groot and Remco H. S. Westerink. ALTEX – Alternatives to animal experimentations. January 2020.

Tukker AM et al. report that the sensitivity of drug-induced effects differed between the human iPSC-derived neuronal lines and that such differences are caused by seeding density, maturation and ratios of inhibitory and excitatory cell types. Furthermore, the author show that all tested models were able to form synaptically connected and bursting active networks and that these models have the potential to be used be used for animal-free in vitro seizure liability assessment. Importantly, the human iPSC-derived neurons were capable of modeling seizure-like activity at the same level or even better than the rat primary cortical neuronal culture.

Read the paper here.

Although we decided to highlight the article by Tukker et al., we selected four scientific articles that delve into the topic of using MEA’s and its technology for drug testing. These can be found below:

  1. Acute in vitro effects on embryonic rat dorsal root ganglion (DRG) cultures by in silico predicted neurotoxic chemicals: Evaluations on cytotoxicity, neurite length, and neurophysiology.
    by  Andrew F.M. Johnstone, Cina M. Mack, Matthew C. Valdez, Timothy J. Shafer, Richard M. LoPachin, David W. Herr and Prasada Rao S. Kodavanti. Toxicology in Vitro. December 2020.
    Read the paper here.
  2. Adult mouse sensory neurons on microelectrode arrays exhibit increased spontaneous and stimulus-evoked activity in the presence of interleukin-6.
    by Bryan J. Black, Rahul Atmaramani, Rajeshwari Kumaraju, Sarah Plagens, Mario Romero-Ortega, Gregory Dussor, Theodore J. Price, Zachary T. Campbell and Joseph J. Pancrazio. Journal of Neurophysiology. September 2018.
    Read the paper here.
  3. Development of an objective index, neural activity score (NAS), reveals neural network ontogeny and treatment effects on microelectrode arrays.
    by Austin P. Passaro, Onur Aydin, M. Taher A. Saif and Steven L. Stice. BioRxiv. July 2020.
    Read the paper here. 
  4. Adaptation of robust Z’ factor for assay quality assessment in microelectrode array based screening using adult dorsal root ganglion neurons.
    by Rahul Atmaramania, Joseph J. Pancrazio and Bryan J. Black. Journal of Neuroscience Methods. June 2020.
    Read the paper here.