| Project/Area Number |
18K15521
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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 52030:Psychiatry-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
Takamatsu Gakuya 琉球大学, 医学(系)研究科(研究院), 助教 (90801431)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 双極性障害 / iPS細胞 / ゲノム医学 / 病態生理 / カルシウムイメージング / 連鎖解析 / 疾患モデル / 神経細胞 / 疾患iPS / 神経分化誘導 / 気分障害 / 疾患ゲノム / ミトコンドリア / ライブイメージング / モデル細胞 / 家系研究 / 精神疾患モデル細胞 |
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| Outline of Final Research Achievements |
Patient-derived induced pluripotent stem cells (iPSCs) with genetic variations having large effects on the development of neuropsychiatric diseases are expected to be cellular disease models. To establish bipolar disorder iPSC model, we focused on rare familial cases with potential high-risk genetic factors and we performed comprehensive genetic analysis and cellular phenotype analysis of patient iPSC-derived neurons.
In summary, we identified SPOCD1, a candidate gene which have the potential to contribute to bipolar disorder and depression in a multiplex pedigree. Moreover, iPSCs from affected individuals of the pedigree were differentiated into excitatory neurons. The neurons from the affected individuals showed higher frequency of the calcium transient compared with neurons from healthy controls. Our results would be promising to the cellular model of bipolar disorder for various applications.
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| Academic Significance and Societal Importance of the Research Achievements |
双極性障害の原因はほとんどわかっていない。そのようななか、本研究では、目標である原因変異の明らかな双極性障害疾患モデルiPS細胞の確立に向けて、期待できる成果を得ることができた。疾患モデルiPS細胞が作成されれば、神経細胞の易興奮性の分子機序の解明や本質的な病態生理に基づく創薬、双極性障害動物モデルの作成など、これまでのボトルネックが解消され、多方面に展望が開ける。疾患モデルiPS細胞の確立に向けて、今後さらに研究を積み重ねていく必要がある。
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