| Project/Area Number |
17K17187
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Prosthodontics/ Dental materials science and
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 睡眠時ブラキシズム / 5-HTR２a / ５－HT２A / 5-HT2a / iPS / 5-HT2A / 歯学 / 遺伝子 |
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| Outline of Final Research Achievements |
The aim of this study were investigate mechanism of SB using patient-specific induced-pluripotent stem cells(iPSCs).
iPSCs were generated from monocytes in blood samples of SB patient, which have SNP rs6313 in 5-HT2A gene, and control patient. Neuronal differentiation from iPSCs was conducted according to a previously reported protocol with slight modification. The expression of 5-HT2A mRNA increased in a time-dependent manner during neuronal differentiation from iPSCs. To distinguish 5-HT2A-positive neurons from negative ones, we generated a lentiviral fluorescent protein-expressing-reporter construct dependent on 5-HT2A promoter activity site for live cell labelling of neurons. To investigate the electrophysiological properties and the responsiveness of 5-HT2A-positive neurons, whole-cell patch-clamp recordings were performed. According to whole-cell patch-clamp, 5-HT2A-positive neurons derived from iPSCs are electrophysiologically active and functionally express 5-HT2A.
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| Academic Significance and Societal Importance of the Research Achievements |
iPSを利用したアプローチにより、倫理的・技術的観点より困難であった睡眠時ブラキシズムの疾患特異モデルが確立される。それにより、睡眠時ブラキシズムの原因究明につながる可能性が示唆され、ひいては睡眠時ブラキシズムの治療薬開発の基盤となり得る研究である。
また、研究過程における産物として、iPS細胞より樹立したセロトニン神経細胞への効率的な分化誘導法がある。脳内のセロトニンの役割として、情動のコントロールの他、睡眠と覚醒、摂食行動など様々である。本研究における恩恵は、ブラキシズム発症メカニズムの解明による歯科領域に留まらず、睡眠・神経系領域の研究に対してこそ大いに貢献すると考えられる。
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