| Project/Area Number |
17H06730
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | Gifu University |
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Principal Investigator |
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| Research Collaborator |
NAKAGAWA Tsutomu
FUKAMIZU Akiyoshi
ISHIDA Junji
KIM Jun-Dal
MURATA Kazuya
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アルギニンメチル化 / グリア / アストロサイト / ミクログリア / RNA-seq / 炎症性サイトカイン / ケモカイン / PRMT1 / 脳・神経 / 発生・分化 |
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| Outline of Final Research Achievements |
PRMT1, a major arginine methyltransferase, plays critical roles in transcription, DNA damage response, and cell proliferation. Although PRMT1 is highly expressed in the central nervous system (CNS), its role has not been studied well. Especially, its role in astrocyte, a major CNS cell type which supports neuronal activity, was uncovered.
To identify astrocytic development by loss of PRMT1 in the CNS, we analyzed neural stem cell-specific PRMT1 conditional knockout (PRMT1-CKO) mice. A comprehensive analysis of gene expression in the developing cortices of PRMT1-CKO mice showed upregulation of inflammatory signaling which is generally mediated by astrocytes and microglia which is another CNS cell type. Histological analyses also revealed that populations of astrocytes and microglia were increased in the brain of PRMT1-CKO mice.
Our results indicate that PRMT1 is essential for the development of astrocytes and also affects microglial development.
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| Academic Significance and Societal Importance of the Research Achievements |
妊婦の感染等により胎児の脳が炎症様の状態（脳白質障害等）を起こすとその後の脳発達に致命的な影響が出ることが知られているが、現在有効な治療法や対策が無い。
本研究は、タンパク質アルギニンメチル化を担う酵素：PRMT1に着目して脳の発達を調べた。脳特異的PRMT1欠損マウスは、発達早期に炎症様応答を示すと共に、その後の脳発達が遅延した。本研究結果はPRMT1が正常な脳発達の際には過剰な炎症を抑制する作用があることを示唆しており、健康な脳の発達を支える分子基盤の一端を明らかにした。
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