Neurotoxicity of environmental chemicals, such as pesticides, is a worldwide concern in human welfare. It is challenging to identify human neurotoxicity by animal tests, due to differences in species, costs, and labor. Human induced pluripotent stem cells (hiPSC)-based in vitro tests might be a valuable method to evaluate chemical neurotoxicity, but the standard procedure, such as cell lines and endpoints, has not been fully understood.
In this study, we examined the neurotoxicity of pyrethroid insecticides using the multielectrode array (MEA) recordings of hiPSC-derived neurons. We exposed the hiPSC-derived neurons XCL-1 to pyrethroid insecticides and performed MEA recordings using MED64-Presto.
Exposure with pyrethroids to hiPSC-derived neurons reduced neural network function, such as spikes per network burst and network burst duration in a dose-dependent manner. RT-PCR analysis revealed the expression of the pyrethroid-sensitive voltage-gated sodium channels (VGSCs) in hiPSC-derived neurons. The half-maximal inhibitory concentrations (IC50s) of the MEA parameters were lower than the 30% effective dosages (ED30s) of motor activity repression obtained from the animal experiments.
Taken together, MEA recordings in network activity of hiPSC-derived neurons could be an effective tool to screen compounds with neurotoxicity.