Comparison of Acute Effects of Neurotoxic Compounds on Network Activity in Human and Rodent Neural Cultures

Saavedra L, Wallace K, Freudenrich TF, Mall M, Mundy WR, Davila J, Shafer TJ, Wernig M, Haag D.

Toxicological Sciences, 2021

Summary:

Recently quantification of neural activity using in vitro models of rodent primary neural cell cultures on multielectrode arrays (MEA) have been used for neurotoxicity screening.  Human induced pluripotent stem cells (hiPSCs) hold the potential to generate neurons for human tissue testing and evaluation of human neural network activity.  Current hiPSC-derived neuron protocols are highly variable in resultant neural activity.  The authors generated excitatory and inhibitory hiPSC-derived neurons independently and co-cultured the neurons with primary human astrocytes at defined ratios.  The resulting co-cultures exhibited neural activity and formed synchronized neural network activity recorded on Axion's MEA platform.  

Compounds with known adverse neuroactive effects, including multiple pesticides, were applied to the human neuron/glia co-cultures as well as rat primary cortical cultures and the acute changes to network activity was recorded.  Both neural culture types showed concentration-dependent effects on multiple neural network activity metrics.