Evaluation and application of the diversity of activity patterns in the population of fragile X syndrome neurons
| Project/Area Number |
19K20683
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | Hiroshima University (2021)
Institute of Physical and Chemical Research (2019-2020) |
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Principal Investigator |
Yuichiro Yada 広島大学, 統合生命科学研究科(理), 研究員 (80805797)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 脆弱X症候群 / 疾患特異的iPS細胞 / 多点電極アレイ / 活動多様性 / 神経細胞 / パターン解析 / 神経同期活動 |
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| Outline of Research at the Start |
脆弱X症候群(FXS)は遺伝性疾患で、学習障害やワーキングメモリ機能の低下などの認知障害を生じる。しかし、そのメカニズムは未だ詳しくは分かっていない。本研究は、FXSの神経細胞集団では活動パターンに異常が生じているという仮説を立て、FXS患者iPS細胞由来の神経細胞の活動を計測し、検証する。また、活動パターンを指標として病態改善に有効な薬剤を探索できる可能性を検討する。
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| Outline of Final Research Achievements |
Fragile X syndrome (FXS) is an inherited disorder that causes learning disabilities and cognitive impairment. The electrophysiological basis that causes the disorder is not fully understood. In this study, we aimed to clarify the electrophysiological abnormalities of FXS using neurons derived from disease-specific iPS cells, multi electrode arrays, and pattern analysis techniques. First, we confirmed that the prepared cell lines has FXS-specific genotypes and phenotypes. Then, neurons derived from FXS patients showed higher firing rates than those from healthy controls. The increased firing rates reported in previous studies were also observed in the cell lines used in this study. In addition, there was variation in the initiation timing of neuronal synchronized bursts between FXS patient-derived and healthy control-derived neurons.
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| Academic Significance and Societal Importance of the Research Achievements |
脆弱X症候群患者ではFMRPタンパクの発現が消失し、シナプス・イオンチャネルで様々なタンパク質が過剰発現する。FMRP消失が認知障害を引き起こす生理的なメカニズムは複雑であり、詳細は明らかでない。本研究においてFXS患者由来iPS細胞およびiPS細胞から分化誘導した神経細胞に対する電気生理計測系・取得した計測データ解析系の構築・基礎的な評価を実施し、使用した細胞でFXSでの電気生理的な異常を同定する手がかりとなるような示唆を得た。
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Report
(4 results)
Research Products
(3 results)
