Molecular and Functional Characterization of Different BrainSphere Models for Use in Neurotoxicity Testing on Microelectrode Arrays

Julia Hartmann, Noah Henschel, Kristina Bartmann, Arif Dönmez, Gabriele Brockerhoff, Katharina Koch and Ellen Fritsche 

Cells, 27 April 2023

 

Scientists use Axion’s next-generation Maestro MEA platform to assess the functionality of BrainSphere models in vitro and determine their fitness for acute neurotoxicity testing. 

Neurotoxicity testing currently relies on animal models, but the practice is high cost, low throughput, and often unreliable due to species differences—leading to widespread calls for improved in vitro testing methods. In this study, scientists apply six different protocols to generate BrainSphere models and compare their functional and molecular characteristics using Axion’s Maestro Pro multielectrode array (MEA) platform and other methods. BrainSpheres are three-dimensional neural spheroids that contain more complex cytoarchitectures than 2D cultures but develop much faster than brain organoids, making them a good candidate for high throughput neurotoxicity screening.  

Using spike sorting on the Maestro MEA, as well as pharmacology, the results showed that neuronal subtypes (glutamatergic, GABAergic, dopaminergic, serotonergic, and cholinergic) can be identified and studied independently, allowing for additional granularity and insight into mechanisms of action for unknown compounds in a new approach called the human multi-neurotransmitter receptor (hMNR) assay. Although the assay was used here to assess potential toxic compounds, the authors suggest it could also be applied to disease modeling and drug development in the future.