| Project/Area Number |
17K16645
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
Fujiwara Sho 大阪大学, 医学系研究科, 特任研究員 (10792484)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脊髄損傷 / ホスホリパーゼ / リゾホスファチジン酸 / 脂質メディエーター / PLA2G6 / 脱髄 / 炎症 / 脂質代謝酵素 / iPLA2β / リゾリン脂質 / PLA2G6遺伝子 |
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| Outline of Final Research Achievements |
The central nervous system contains various membrane phospholipids, which are maintained by the metabolic enzymes. Phospholipases A2 (PLA2) are enzymes that hydrolyze glycerophospholipids to produce free fatty acids and lysophospholipids, the precursors of mediators of tissue damage and inflammation. In this study, we focused on the PLA2G6 gene, which is the causative gene of hereditary neurodegenerative diseases. Locomotor function in the KO mouse significantly recovered after SCI and the cavity formation at the injury site was significantly reduced in the KO mouse. In addition, mass spectrometry in the injured spinal cord showed that lysophosphatidic acid were decreased in KO mice, suggesting that they are involved in the exacerbation of the secondary injury of spinal cord.
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| Academic Significance and Societal Importance of the Research Achievements |
脊髄損傷の治療法は、これまでに抗炎症作用と神経保護作用を有した薬剤等の臨床研究が終了しているが、有効性を示すデータには至ってない。本研究では損傷脊髄における細胞膜脂質代謝の破綻に注目し、脂質代謝酵素のノックアウトマウスを用いて、リゾホスファチジン酸が脊髄損傷亜急性期の増悪に関与している可能性があることを示した。この分子機構の解明は脊髄損傷に対する創薬開発の基盤となることが期待できる。
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