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Increased excitability of human iPSC-derived neurons in HTR2A variant-related sleep bruxism
- Source :
- Stem Cell Research, Vol 59, Iss , Pp 102658- (2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 18735061
- Volume :
- 59
- Issue :
- 102658-
- Database :
- Directory of Open Access Journals
- Journal :
- Stem Cell Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.229fdb852f24dda82cebbd84c52c720
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.scr.2022.102658