A study on abnormal cerebrovascular function and accelerated inflammation in the developing brain with Down syndrome
| Project/Area Number |
18K06940
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ダウン症候群 / 神経新生 / 網羅的遺伝子発現解析 / 炎症 / 脳マクロファージ / 炎症細胞 / 脳発達 / 血管 / モデルマウス / 血管形成 / ミクログリア / ダウン症 / 発達遅滞 |
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| Outline of Final Research Achievements |
Down syndrome (DS), is the most common genetic cause of intellectual disability that is assumed to be associated with delayed brain development. The aim of this research project is to understand the mechanisms underlying the delayed brain development in DS. For this purpose, a comprehensive expression analysis of genes was employed. DNA microarray analysis revealed that inflammation-related genes are increased in expression, and flowcytometric analysis revealed that increased expression of inflammation-related genes is caused by increased number of inflammatory cells. Furthermore, we demonstrated that triplication of the Erg gene resulted in increased number of inflammatory cells. Separately, we also identified a decreased expression of Tbx1 gene, which related to brain angiogenesis, in the brain of DS mouse models. Although we failed to detect an abnormal brain-vasculature in DS embryos, we proposed that Erg and Tbx1 genes are assumed to play a role in DS intellectual disability.
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| Academic Significance and Societal Importance of the Research Achievements |
ダウン症の知的障害の原因などは全く分かっていなかったが、我々は、新しくダウン症の脳発達の遅れや知的障害に関係していると思われる遺伝子としてErg遺伝子とTbx1遺伝子を発見した。特に、Erg遺伝子では、胎児期の脳発達の遅れの原因とされる神経新生の低下の原因であることもマウスを用いた実験で明らかにしたことは、ダウン症の知的障害の胎内治療の実現化において重要な知見であると考えている。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome.2020
Author(s)
Ishihara K, Shimizu R, Takata K, Kawashita E, Amano K, Shimohata A, Low D, Nabe T, Sago H, Alexander WS, Ginhoux F, Yamakawa K, Akiba S.
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Journal Title
Brain Pathology
Volume: 30
Issue: 1
Pages: 75-91
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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