High-throughput screening using iPSC-derived GABAergic neurons to elucidate disease-relevant phenotypes in serotonin 2A receptor gene variant-related sleep bruxism
| Project/Area Number |
21K21049
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0907:Oral science and related fields
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| Research Institution | Showa University |
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Principal Investigator |
サルカル アビジットクマール 昭和大学, 歯学部, ポストドクター (40908737)
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| Project Period (FY) |
2021-08-30 – 2022-03-31
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| Project Status |
Discontinued (Fiscal Year 2021)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | iPSC-derived neurons / sleep bruxism / excitability / Sleep bruxism / iPS cell / GABAergic neurons / transcriptomic analysis / MEA array |
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| Outline of Research at the Start |
Examination of disease-relevant phenotypes by morphological and transcriptomic analysis- Establish iPSCs, Differentiate iPSCs into target 5HT2AR expressing GABAergic neurons, Morphological analysis, Transcriptomic analysis. Investigation of SB patient-specific phenotypes by multielectrode array (MEA) recordings
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| Outline of Annual Research Achievements |
The consequences of sleep bruxism (SB) appear to be serious orofacial pain and several dysfunction conditions, which seriously compromises the patient’s quality of life. However, the definitive mechanisms that promote SB are not well understood. We previously found a variant in the neuronal serotonin 2A receptor gene (HTR2A), rs6313 associated with the risk of SB and established human induced pluripotent stem cell (iPSC)-derived neurons from SB patients with this genetic variant. It has been suggested that attenuating activity of serotonin 2A receptor (5-HT2AR)-expressing GABAergic neurons during sleep may be involved in the mechanism of SB development. We found altered excitability in SB iPSC-derived neurons in the early stage of neurogenesis. This year we established two additional iPSC lines from a SB patient (SB3) and an unaffected control (C3) subject. In addition, we performed functional investigations of the SNP neurons at DIV31-51, 52-71, 72-91, and 92-111 of neurogenesis. We revealed that SB neurons showed significantly higher action potential firing frequency, higher gain, and shorter action potential half duration than control neurons over the course of DIV111 in culture. The altered electrophysiological properties of SB neurons indicate that affected cells may be hyperactive.
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Report
(1 results)
Research Products
(5 results)
