ヒトiPS細胞由来神経細胞における解離性麻酔剤の神経毒性評価

抄録

The assessment of neurotoxicity of illicit drugs currently depends on electrophysiological tests using animal brain slices and animal behavioral tests but with limited predictivity for human outcomes and high costs. Furthermore, to screen the neurotoxicity of many illicit drugs, it is expected to reduce animal studies and use convenient, high-throughput in vitro testing approaches. Ketamine, a narcotic-designated dissociative anesthetic, has been reported to suppress electrophysiological activity in rat brains and cultured neurons via NMDA receptor inhibition. In the present study, we examined the pharmacological effect of dissociative anesthetics using human iPS cells (iPSC) -derived neurons to establish a new approach for neurotoxicity assessment. Multi-electrode array (MEA) system revealed that treatment with ketamine decreased spike numbers and inhibited network bursts of iPSC-derived neurons. The other dissociative anesthetics phencyclidine and methoxetamine, which inhibit NMDA receptor, also suppressed neural activities of iPSC-derived neurons. These data suggest that of iPSC-derived neurons can detect neural network inhibition by dissociative anesthetics. Thus, MEA recordings of iPSC-derived neuron activities could be an effective tool for elucidating drug-induced neurotoxicity.