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

Stem Cell Research

Wado Akamatsu¹  Takahiro Shiga¹  Shiro Nakamura²  Tomio Inoue²  Yurie Hoashi³  Yuka Abe³  Avijite Kumer Sarkar³  Taro Sato³  Kento Nakai³  Kazuyoshi Baba³ 

[1] Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan;Department of Prosthodontics, Showa University School of Dentistry, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan;

关键词: Sleep bruxism;    Human induced pluripotent stem cells;    Patch-clamp technique;    Intrinsic membrane properties;    iPSC-derived neuronal maturation;    Altered excitability;   

DOI  :  

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown