Investigation of GABAergic neuronal function using sleep bruxism-specific iPSCs

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K09709
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57050:Prosthodontics-related
• Research Institution: Showa University
• Principal Investigator: Abe Yuka 昭和大学, 歯学部, 講師 (80614156)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 睡眠時ブラキシズム / 疾患特異的iPS細胞

Outline of Final Research Achievements

This study aimed to find functional phenotypic differences at the cellular level involved in neurotransmission in sleep bruxism. Using a single nucleotide polymorphism of the serotonin 2A receptor gene as a risk allele, induced pluripotent stem cells (iPSCs) from patients with sleep bruxism and controls were established. Then, neuronal cells were differentiated from the iPSCs, which were thought to contain GABAergic neurons. Comparative electrophysiological studies of the neurons revealed passive and active electrophysiological membrane properties similar to those of the formation of neuronal polarity in vivo. In addition, neurons derived from patients with sleep bruxism showed lower action potential rheobase and prolonged APD50, the duration of repolarization to 50% of the action potential amplitude.

Free Research Field

歯科補綴学

Academic Significance and Societal Importance of the Research Achievements

疾患特異的iPS細胞由来神経細胞を用いることで，生体内の細胞レベルの情報伝達機構の解明にアプローチすることが可能であり，これにより，従来困難であった睡眠時ブラキシズム患者の生体内で生じる発生メカニズムが解明されることが期待できる．本研究の成果はその端緒となるものであり，睡眠時ブラキシズムを有する患者と有しない健康成人では，神経伝達の基電流が低値を示し，かつ活動電位の振幅の50％まで再分極するまでの持続時間が延長していたことから，抑制性の神経伝達の変化が睡眠時ブラキシズム発症に関連する可能性がある．さらに解明を進めていくことで，将来，創薬や病態解明に寄与することができると考えられる．