Neurotoxicity of anesthetics in the developing neurons: in vitro model to assess the neurotoxicity in human induced pluripotent stem cell derived neurons.

Research Project

Project/Area Number	25670666
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Anesthesiology
Research Institution	Tokyo Medical and Dental University
Principal Investigator	MAKITA Koshi 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (20199657)
Co-Investigator(Renkei-kenkyūsha)	ITO Hiroyuki 東京医科歯科大学, 医学部附属病院, 助教 (80595554) UCHIDA Tokujiro 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (40262183)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000) Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	iPS細胞由来神経細胞 / 麻酔薬 / 毒性評価 / ケタミン / ミトコンドリア / アポトーシス / iPS細胞 / 神経幹細胞 / 麻酔薬毒性 / 幼弱脳 / 活性酸素種
Outline of Final Research Achievements	To study the toxic effect of anesthetic drugs on human neurons, an experimental model using cultured neurons derived from human induced pluripotent stem cells (iPSCs) was examined, and the mechanisms of their toxicity were studied. We studied ketamine toxicity in this study, and we established an in vitro model to assess the neurotoxicity in iPSC-derived neurons. The present data indicate that initial mitochondrial dysfunction and autophagy may be resulted from inhibitory effect of ketamine on the mitochondrial electron transport system. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons, and these mechanisms underlie ketamine-induced neural toxicity.