Increased excitability of human iPSC-derived neurons in HTR2A variant-related sleep bruxism

• DOI: 10.1016/j.scr.2022.102658
• Publication Date: 2022-01-03T23:52:37Z
• Authors: Avijite Kumer Sarkar; Shiro Nakamura; Kento Nakai; Taro Sato; Takahiro Shiga; Yuka Abe; Yurie Hoashi; Tomio Inoue; Wado Akamatsu; Kazuyoshi Baba
• Keywords: Sleep

Sleep bruxism (SB) is a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep. We previously found significant association between SB single nucleotide polymorphism (SNP), rs6313, in neuronal serotonin 2A receptor gene (HTR2A), established human induced pluripotent stem cell (iPSC)-derived neurons from patients with genetic variant. To elucidate electrophysiological characteristics iPSC-derived neural cells bearing an SB-related variant, we generated ventral hindbrain unaffected controls, explored intrinsic membrane properties these using patch-clamp technique. that mature time-dependent manner long-term control cultures. exhibited higher action potential firing frequency, gain, shorter half duration. This first vitro modeling patient-specific iPSCs. The revealed may serve as benchmark for further investigation pathogenic mechanisms underlying SB. Moreover, our results on cultures provide strategy to define functional maturity vitro, which can be implemented research neurogenesis, neurodevelopmental disorders.