Seizure is one of the major causes of the cessation of development of central nervous system drugs. Multielectrode array (MEA) system has advantages in high-throughput neurotoxicity tests. Although rat behavioral tests are mainly used to evaluate neurotoxicity in drug development, it is challenging to identify human neurotoxicity by animal tests due to differences in species.
Human induced pluripotent stem cells (hiPSC)-based experiment might be valuable to evaluate human neurotoxicity. In this study, we examined the neurotoxicity of fluoxetine by MEA using hiPSC-derived neurons. We exposed the hiPSC-derived neurons XCL-1 to the drug and performed MEA recordings using MED64-Presto.
Exposure of fluoxetine to hiPSC-derived neurons reduced neural network activity, such as the number of spikes and network bursts in a dose-dependent manner. In rat cortical neurons, the network activities were also reduced by fluoxetine in a comparable dose-dependent manner to hiPSC-derived neurons.
MEA recordings in network activity of hiPSC-derived neurons could be an effective tool for neurotoxicity screening in drug development.