| Project/Area Number |
17K10931
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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 |
Orthopaedic surgery
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| Research Institution | Hiroshima University |
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Principal Investigator |
Kamei Naosuke 広島大学, 病院(医), 准教授 (70444685)
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| Co-Investigator(Kenkyū-buntansha) |
味八木 茂 広島大学, 病院(医), 講師 (10392490)
安達 伸生 広島大学, 医系科学研究科(医), 教授 (30294383)
石川 正和 広島大学, 医系科学研究科(医), 寄附講座准教授 (60372158)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 脊髄損傷 / 小胞体ストレス / OASIS / グリオーシス / 脊椎脊髄病学 |
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| Outline of Final Research Achievements |
The purpose of this study was to investigate the relationship between endoplasmic reticulum (ER) stress mediated by old astrocyte specifically induced substance (OASIS) and astrogliosis in spinal cord injury (SCI). We used siRNA of OASIS and mice deficient for OASIS in SCI models. In a mouse model of spinal cord contusion injury, a significant increase in OASIS mRNA on day 7 and an increase in protein on days 7 and 14 was observed in injured spinal cords. Furthermore, siRNA injection inhibited astrogliosis and hindlimb motor function recovery. On the other hand, functional recovery was better in the OASIS-deficient mice than in the wild-type mice after SCI. OASIS deletion did not inhibit astrocyte migration but reduced the excessive accumulation of N-cadherin-expressing reactive astrocytes that formed the glial scar around the injury site. In addition, OASIS deletion increased the number of serotonin-positive axons in spinal cord regions caudal to the injury site.
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| Academic Significance and Societal Importance of the Research Achievements |
損傷された脊髄が再生しないと言われている最大の原因がグリア瘢痕の形成であると考えられている。そのグリア瘢痕が形成されるメカニズムにOASISを介した小胞体ストレス応答が関与していることが本研究で明らかとなった。本研究における知見を発展させてOASISを介した小胞体ストレス応答のコントロールによってグリア瘢痕を抑制することができれば、脊髄損傷の治療開発におけるブレイクスルーとなり、新たな治療ターゲットとなり得る。
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