Investigation of neurotransmission mechanism related to serotonin in neurons derived from sleep bruxism induced pluripotent stem cells

• Project/Area Number: 15K20454
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Showa University
• Principal Investigator: Abe Yuka 昭和大学, 歯学部, 講師 (80614156)
• Research Collaborator: NAKAI Kento ; NAKAZATO Yukari
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 睡眠時ブラキシズム / iPSC / セロトニン / iPS細胞 / SNP / 遺伝子多型 / セロトニン神経系

Outline of Final Research Achievements

Mechanical stress of sleep bruxism (SB) is known to be responsible for poor prognosis of dental treatment and seriously compromises patients’ quality of life, although the etiology of SB remains incompletely understood. The aim of this study is to elucidate the functional difference of 5-HT 2A receptor positive neurons between C and T allele carriers using electrophysiological recording of iPSC-derived neurons. Human iPSCs from SB and healthy controls were differentiated into neurons with the characteristics of the ventral hindbrain, where 5-HT2A positive neurons are enriched. By using qRT-PCR and immunostaining, we confirmed that iPSCs were successfully differentiated into 5-HT 2A receptor positive neurons. In the whole-cell patch-clamp recordings, the differentiated neurons generated repetitive action potentials in response to inward currents. These functional observations suggested that neurons differentiated from patient-specific iPSCs contained 5-HT 2A receptor positive neurons.

Academic Significance and Societal Importance of the Research Achievements

睡眠中の歯ぎしりが生じると，歯や顎に様々なトラブルが生じますが，現在のところ，歯ぎしりの発生するメカニズムはわかっていません．メカニズムが解明できれば，現在あるものよりも有効な治療法を考えることができ，歯科治療の選択肢が広がります．この研究は，iPS細胞技術を用いて歯ぎしりに関連する遺伝的な要因をもった神経細胞を作って調べたもので，その神経細胞が一定の活動電位を発生することが確認されました．この研究が将来さらに進めば，新たな治療法開発に繋がると考えています．

Research Products

• [Journal Article] Generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism (2017)
  • Author(s): Hoashi Y, Okamoto S, Abe Y, Matsumoto T, Tanaka J, Yoshida Y, Imaizumi K, Mishima K, Akamatsu W, Okano H, Baba K
  • Journal Title: Journal of Prosthodontic Research Volume: 61 Issue: 3 Pages: 242-250
  • DOI: 10.1016/j.jpor.2016.11.003
  • NAID: 130006076280
  • ISSN: 1883-1958, 1883-9207
  • Peer Reviewed
• [Journal Article] Association between patterns of jaw motor activity during sleep and clinical signs and symptoms of sleep bruxism. (2016)
  • Author(s): Yoshida Y, Suganuma T, Takaba M, Ono Y, Abe Y, Yoshizawa S, Sakai T, Yoshizawa A, Nakamura H, Kawana F, Baba K.
  • Journal Title: J Sleep Res. Volume: 印刷中 Issue: 4 Pages: 415-421
  • DOI: 10.1111/jsr.12481
  • Peer Reviewed
• [Journal Article] Effects of citalopram on jaw-closing muscle activity during sleep and wakefulness in mice (2016)
  • Author(s): Ikawa Y, Mochizuki A, Katayama K, Kato T, Ikeda M, Abe Y, Nakamura S, Nakayama K, Wakabayashi N, Baba K, Inoue T
  • Journal Title: Neurosci Res Volume: 113 Pages: 48-55
  • DOI: 10.1016/j.neures.2016.07.004
  • Peer Reviewed
• [Journal Article] チェアサイドとベッドサイドをつなぐ睡眠時ブラキシズムの診断と治療 睡眠時ブラキシズム臨床診断の現状と展望 (2016)
  • Author(s): 馬場一美, 安部友佳
  • Journal Title: 日本補綴歯科学会誌 Volume: 8 Pages: 153-158
  • Peer Reviewed
• [Journal Article] 睡眠時ブラキシズム臨床診断の現状と展望 (2016)
  • Author(s): 馬場一美、安部友佳
  • Journal Title: 日本補綴歯科学会誌 Volume: 8 Pages: 153-158
  • NAID: 130005153764
• [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，小溪啓介，帆足有理恵，松本貴志，安部友佳，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] In vitro disease modeling for sleep bruxism using induced pluripotent stem cells (2017)
  • Author(s): Tozawa Yurie, Nakai Kento, Yoneima Kazuaki, Tanaka Junichi, Matsumoto Takashi, Abe Yuka, Imaizumi Kento, Mishima Kenji, Akamatsu Wado, Okano Hideyuki, Baba Kazuyoshi
  • Organizer: 65th Annual Meeting of Japanese Association for Dental Research
  • Int'l Joint Research
• [Presentation] Accuracy of newly developed portable PSG device for detection of sleep bruxism-related masseter EMG muscle activity (2017)
  • Author(s): Nakazato Yukari，Takaba Masayuki，Yoshida Yuya，Abe Yuka，Ono Yasuhiro，Yoshizawa Shuichiro，Nakamura Hirotaka，Kawana Fusae，Suganuma Takeshi，Kato Takafumi，Baba Kazuyoshi
  • Organizer: 14th World Sleep 2017, Joint Congress of World Association of Sleep Medicine and World Sleep Federation
  • Int'l Joint Research
• [Presentation] 簡易睡眠検査装置による睡眠時ブラキシズムの測定 (2017)
  • Author(s): 中里友香理，高場雅之，吉田裕哉，安部友佳，小野康寛，葭澤秀一郎，中村浩崇，菅沼岳史，馬場一美
  • Organizer: 第30回日本顎関節学会学術大会
• [Presentation] トップジャーナルに採択される臨床研究に求められるものとは？ (2016)
  • Author(s): 安部友佳
  • Organizer: 公益社団法人日本補綴歯科学会第125回学術大会
  • Place of Presentation: 金沢
  • Year and Date: 2016-07-08
• [Presentation] iPS細胞を使用した5-HT2A遺伝子多型をもつ新規睡眠時ブラキシズムモデル (2016)
  • Author(s): 帆足有理恵, 岡本理史，安部友佳，松本貴志，田中準一，吉田裕哉，今泉研人，美島健二 ，赤松和土，岡野栄之，馬場一美
  • Organizer: 日本補綴歯科学会第125回学術大会
  • Place of Presentation: 石川
  • Year and Date: 2016-07-08
• [Presentation] トップジャーナルに採択される臨床研究に求められるものとは？ (2016)
  • Author(s): 安部友佳
  • Organizer: 日本補綴歯科学会第125回学術大会
  • Place of Presentation: 石川
  • Year and Date: 2016-07-08
  • Invited
• [Presentation] 振動刺激による睡眠時ブラキシズム抑制効果の検証 (2016)
  • Author(s): 中村浩崇，小野康寛，吉田裕哉，安部友佳，高場雅之，菅沼岳史，葭澤秀一郎，中里友香理，馬場一美
  • Organizer: 第41回日本睡眠学会定期学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-07-07
• [Presentation] Establishment of Human Sleep Bruxism Model by Induced Pluripotent Stem Cells. (2016)
  • Author(s): Tozawa Y, Okamoto S, Abe Y, Matsumoto T, Tanaka J, Yoshida Y, Imaizumi K, Mishima K, Akamatsu W, Okano H, Baba K
  • Organizer: 94th General Session & Exhibition of the IADR
  • Place of Presentation: Seoul, Republic of Korea
  • Year and Date: 2016-05-22
  • Int'l Joint Research
• [Presentation] iPS細胞を用いた5-HT2A遺伝子多型をもつ睡眠時ブラキシズムモデルの確立 (2016)
  • Author(s): 帆足有理恵，岡本理史，安部友佳，松本貴志，田中準一，吉田裕哉，今泉研人，美島健二，赤松和土，岡野栄之，馬場一美
  • Organizer: 公益社団法人日本補綴歯科学会第125回学術大会
  • Place of Presentation: 金沢
• [Presentation] 簡易睡眠検査装置による睡眠時ブラキシズムの測定 (2016)
  • Author(s): 中里友香理，高場雅之，吉田裕哉，安部友佳，小野康寛，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: 日本補綴歯科学会東京支部 第20回学術大会
  • Place of Presentation: 東京
• [Presentation] 睡眠時ブラキシズム研究の最前線 (2016)
  • Author(s): 安部友佳
  • Organizer: 東京医科歯科大学大学院 睡眠制御学講座 第6回快眠セミナー
  • Place of Presentation: 東京
  • Invited
• [Presentation] Establishment of Human Sleep Bruxism Model by Induced Pluripotent Stem Cells(iPSCs). (2015)
  • Author(s): Hoashi Y, Okamoto S , Matumoto T, Yoshida Y, Tanaka J, Imaizumi K, Abe Y, Akamatu W, Okano H, Mishima K, Baba K
  • Organizer: 4th Asian Academic Congress for Temporomandibular Joint
  • Place of Presentation: Manila, Philippine
  • Year and Date: 2015-11-16
  • Int'l Joint Research
• [Presentation] Serotonin receptor gene polymorphism in sleep bruxism: a polysomnographic study. (2015)
  • Author(s): Abe Y, Hoashi Y, Yoshida Y, Yoshizawa S, Sakai T, Suganuma T, Takaba M, Ono Y, Yoshizawa A, Nakamura H, Kawana F, Baba K
  • Organizer: 16th Biennial Meeting of the International College of Prosthodontists
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] PSGによる睡眠時ブラキシズム臨床診断法の検証. (2015)
  • Author(s): 吉田裕哉，葭澤秀一郎，酒井拓郎，菅沼岳史，高場雅之，小野康寛，安部友佳，吉澤亜矢子，中村浩崇，川名ふさ江，馬場一美
  • Organizer: 第7回ISMSJ（Integrated Sleep Medicine Society Japan）学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-31
• [Presentation] 睡眠ポリグラフによる睡眠時ブラキシズム臨床診断法の検証. (2015)
  • Author(s): 吉田裕哉，葭澤秀一郎，酒井拓郎，菅沼岳史，高場雅之，小野康寛，安部友佳，吉澤亜矢子，中村浩崇，川名ふさ江，馬場一美
  • Organizer: 第40回日本睡眠学会 定期学術集会
  • Place of Presentation: 栃木
  • Year and Date: 2015-07-02
• [Presentation] 睡眠時ブラキシズム臨床診断基準の検証 ー筋活動パターンと臨床徴候の関連ー (2015)
  • Author(s): 吉田裕哉，葭澤秀一郎，酒井拓郎，菅沼岳史，高場雅之，小野康寛，安部友佳，吉澤亜矢子，中村浩崇，川名ふさ江，馬場一美
  • Organizer: 日本補綴歯科学会第124回学術大会
  • Place of Presentation: 埼玉
  • Year and Date: 2015-05-30
• [Book] パーシャルデンチャー治療 失敗回避のためのポイント47 (2017)
  • Author(s): 山下秀一郎、佐々木啓一、鱒見進一、谷田部 優、馬場一美、服部佳功，安部友佳
  • Total Pages: 240
  • Publisher: クインテッセンス出版
  • ISBN: 9784781205854
• [Remarks] Lilitory: 昭和大学学術業績リポジトリ
  • URL: https://meta.lilitory.showa-u.ac.jp
• [Remarks] Lilitory 昭和大学学術業績リポジトリ
  • URL: http://meta.lilitory.showa-u.ac.jp/