Host: The Japanese Society of Toxicology
Name : The 47th Annual Meeting of the Japanese Society of Toxicology
Date : 2020 -
There are concerns that industrial chemicals cause developmental neurotoxicity (DNT), leading to neurobehavioral outcomes, such as learning disabilities and cognitive impairment. Compared to the adult brain, the fetal brain is inherently more susceptible to compound-induced toxicity. Thus, exposure to these substances during early development may lead to adverse neurological effects manifested at a later phase of life. Because current DNT guideline (OECD TG426) requires a lot of animals and costs, it is necessary to establish an in vitro DNT method with more accurate and better predictability. Due to complex processes of cell development and maturation in human brain, human iPS cells (hiPSCs) are expected to provide a novel human cell-based assay systems as alternative in vitro testing approaches. Pyrethroids has been reported to show DNT in rodents. In the present study, we evaluated chemicals with DNT risk using microelectrode array (MEA) system and searched a suitable functional endpoint. Treatment with pyrethroids, such as deltamethrin, inhibited spike numbers and network bursts using MEA recordings of hiPSC-derived neurons. These data suggest that pyrethroids induce neurotoxicity by inhibiting neural network. Taken together, MEA recordings could be an effective tool for elucidating chemical-induced neurotoxicity.
