Investigation of GABAergic neuronal function using sleep bruxism-specific iPSCs

• 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
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 睡眠時ブラキシズム / 疾患特異的iPS細胞 / iPS細胞 / GABA作動性ニューロン

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.

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．

Research Products

• [Journal Article] Increased excitability of human iPSC-derived neurons in HTR2A variant-related sleep bruxism (2022)
  • Author(s): Sarkar Avijite Kumer、Nakamura Shiro、Nakai Kento、Sato Taro、Shiga Takahiro、Abe Yuka、Hoashi Yurie、Inoue Tomio、Akamatsu Wado、Baba Kazuyoshi
  • Journal Title: Stem Cell Research Volume: 59 Pages: 102658-102658
  • DOI: 10.1016/j.scr.2022.102658
  • Peer Reviewed / Open Access
• [Journal Article] 顎口腔系の睡眠関連運動障害評価のウェアラブルシステムと将来像 (2022)
  • Author(s): 馬場一美，安部友佳
  • Journal Title: 睡眠医療 Volume: 16 Pages: 51-57
• [Journal Article] In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells (2021)
  • Author(s): Nakai Kento、Shiga Takahiro、Yasuhara Rika、Sarkar Avijite Kumer、Abe Yuka、Nakamura Shiro、Hoashi Yurie、Kotani Keisuke、Tatsumoto Shoji、Ishikawa Hiroe、Go Yasuhiro、Inoue Tomio、Mishima Kenji、Akamatsu Wado、Baba Kazuyoshi
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 15437-15437
  • DOI: 10.1038/s41598-021-95041-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of a contingent vibratory stimulus delivered by an intra-oral device on sleep bruxism: a pilot study (2019)
  • Author(s): Nakamura Hirotaka、Takaba Masayuki、Abe Yuka、Yoshizawa Shuichiro、Suganuma Takeshi、Yoshida Yuya、Nakazato Yukari、Ono Yasuhiro、Clark Glenn T.、Baba Kazuyoshi
  • Journal Title: Sleep and Breathing Volume: 23 Issue: 1 Pages: 363-372
  • DOI: 10.1007/s11325-019-01782-x
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Sleep bruxism: a novel approach to elucidate the mechanism using a disease-specific iPSC-based model (2021)
  • Author(s): Abe Yuka
  • Organizer: 19th Biennial Meeting of the International College of Prosthodontists conference
  • Int'l Joint Research / Invited
• [Presentation] Electrophysiological characterization of sleep bruxism patient-specific hiPSC-derived neurons (2021)
  • Author(s): Avijite Kumer Sarkar, Shiro Nakamura, Kento Nakai, Rika Yasuhara, Takahiro Shiga, Yuka Abe, Yurie Hoashi, Keisuke Kotani, Tomio Inoue, Kenji Mishima, Wado Akamatsu, Kazuyoshi Baba
  • Organizer: The 7th Biennial Joint Congress of JPS-CPS-KAP
  • Int'l Joint Research
• [Presentation] Electrophysiological characterization of sleep bruxism patient-specific induced pluripotent stem cell-derived neurons (2020)
  • Author(s): Avijite Kumer Sarkar, Shiro Nakamura, Yuka Abe, Kento Nakai, Rika Yasuhara, Takahiro Shiga, Yurie Hoashi, Keisuke Kotani, Tomio Inoue, Kenji Mishima, Wado Akamatsu, Kazuyoshi Baba
  • Organizer: 日本顎口腔機能学会第64回学術大会
• [Presentation] Patch-clamp recordings of neurons induced from sleep bruxism patient-specific iPSCs (2019)
  • Author(s): Nakai K, Abe Y, Hoashi Y, Nakamura S, Shiga T, Avijite K S, Yasuhara R, Matsumoto T, Kotani K, Inoue T, Mishima K, Akamatsu W, Baba K
  • Organizer: 97th General Session & Exhibition of the IADR
  • Int'l Joint Research
• [Presentation] Electrophysiological recordings of neurons derived from sleep bruxism patient-specific iPSCs (2019)
  • Author(s): Nakai K, Abe Y, Shiga T, Hoashi Y, Nakamura S, Avijite K S, Yasuhara R, Matsumoto T, Kotani K, Inoue T, Mishima K, Akamatsu W, Baba K
  • Organizer: ISSCR 2019 Annual Meeting
  • Int'l Joint Research
• [Presentation] 睡眠時ブラキシズム特異的iPS細胞由来GABA作動性神経細胞の電気生理学的評価 (2019)
  • Author(s): 中井健人, 安部友佳, 帆足有理恵, Avijite Kumer Sarkar, 小溪啓介, 松本貴志, 安原理佳, 美島健二, 中村史朗, 井上富雄, 志賀孝宏, 赤松和土, 馬場一美
  • Organizer: 日本補綴歯科学会 第128回学術大会
• [Presentation] 携帯型睡眠検査装置による睡眠時ブラキシズム記録の妥当性検証 (2018)
  • Author(s): 中里友香理，高場雅之，吉田裕哉，安部友佳，葭澤秀一郎，中村浩崇，川名ふさ江，菅沼岳史，加藤隆史，矢谷博文，馬場一美
  • Organizer: 日本顎口腔機能学会 第60回学術大会
• [Book] Section III Sleep bruxism: from oral behavior to disorder 28. Genetic and environmental factors in SB. / Sleep Medicine for Dentists: An Evidence-Based Overview, Second Edition (2020)
  • Author(s): Baba K, Abe Y, Khoury S, Lobbezoo F
  • Total Pages: 240
  • Publisher: Quintessence Publishing USA
  • ISBN: 9780867158281
• [Remarks] 昭和大学研究者情報・業績集
  • URL: https://researchers-achievements.showa-u.ac.jp/
• [Remarks] 昭和大学研究者情報・業績集
  • URL: https://researchers-achievements.showa-u.ac.jp
• [Remarks] Lilitory: 昭和大学学術業績リポジトリ
  • URL: https://meta.lilitory.showa-u.ac.jp