Development of drug evaluation system in cultured human iPSC derived neuronal network which evoked sleep-awake rhythm

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K20111
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering and related fields
• Research Institution: Tohoku Institute of Technology
• Principal Investigator: SUZUKI IKURO 東北工業大学, 大学院工学研究科, 准教授 (90516311)
• Co-Investigator(Kenkyū-buntansha): 辛島 彰洋 東北工業大学, 工学部, 准教授 (40374988)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: iPS / 睡眠 / 覚醒 / アミン・コリン / 徐波 / LTD / 睡眠恒常性仮説 / MEA

Outline of Final Research Achievements

The cross-regional neurons in the brainstem, hypothalamus, and thalamus regulate the central nervous system, including the cerebral cortex, in a sleep-wake cycle-dependent manner. A characteristic brain wave, called slow wave, of about 1 Hz is observed during non-REM sleep, and the sleep homeostasis hypothesis proposes that the synaptic connection of a neural network is weakened during sleep. In the present study, we found that sleep-wake states can be mimicked by cyclic neuromodulator administration and show that LTD-like phenomena can be induced by 1 Hz low-frequency stimulation (LFS) in in vitro human iPSC-derived neurons. These results could be applied in studies on the mechanism of slow waves during sleep or in an in vitro drug efficacy evaluation depending on sleep-wake state.

Free Research Field

iPS細胞の非臨床創薬応用

Academic Significance and Societal Importance of the Research Achievements

Neuromodulatorや電気刺激によって、ヒトiPS細胞由来ニューロンに睡眠・覚醒状態を惹起させる本研究成果は、睡眠中の徐波のメカニズム研究や生体現象を模倣した睡眠覚醒状態依存的なin vitro薬効評価に応用することができると考えられる。