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

2018 Fiscal Year Final Research Report

• 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
• Keywords: 睡眠時ブラキシズム / iPSC / セロトニン

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.

Free Research Field

補綴歯科学

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．