| Project/Area Number |
16K09220
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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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| Research Field |
Legal medicine
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Shimada Ryo 東京女子医科大学, 医学部, 講師 (10376725)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 細胞老化 / 老化関連酸性ベータガラクトシダーゼ / Cyclin D1 / PCNA / p16 / p21 / p53 / β-ガラクトシダーゼ / cyclin D1 / 社会医学 / 法医学 / 法医病理学 |
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| Outline of Final Research Achievements |
This study aims to clarify how the mRNA and protein expression of different markers of cell cycle and senescence are modulated and switched over time after TBI. We performed SA-β-gal staining and examined the time-dependent changes in expression levels of proteins and mRNA, related to cell cycle and cellular senescence markers, in the cerebrum during the initial 14 days after TBI using a mouse model of CCI. Within the area adjacent to the cerebral contusion after TBI, the protein and/or mRNA expression levels of cell cycle markers were increased significantly until 4 days after injury and senescence markers were significantly increased at 4, 7, and 14 days after injury. Our findings suggested that TBI initially activated the cell cycle in neurons, astrocytes, and microglia within the area adjacent to the hemicerebrum contusion in TBI, whereas after 4 days, such cells could undergo senescence in a cell-type-dependent manner.
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| Academic Significance and Societal Importance of the Research Achievements |
外傷性脳損傷はアポトーシスなどにより神経細胞死を生じる。一方、老化細胞が炎症性サイトカインや細胞外マトリックス分解酵素などの分泌性タンパク質を発現し、生体に傷害をもたらす。老化細胞は老化細胞マーカーの発現と共に、一旦活性化された細胞周期の抑制を特徴としている。本研究では、外傷性脳損傷後に神経細胞死や炎症をきたす機序に細胞老化が関係していると分かった。細胞老化の抑制は神経細胞を保護する可能性が示唆された。また、老化関連酸性ベータガラクトシダーゼ測定キットを用い、脳損傷を診断することができると示唆され、法医学的及び病理学的診断に寄与できた。
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