| Project/Area Number |
15H04595
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Veterinary medical science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
Kuwamura Mitsuru 大阪府立大学, 生命環境科学研究科, 准教授 (20244668)
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| Co-Investigator(Kenkyū-buntansha) |
井澤 武史 大阪府立大学, 生命環境科学研究科, 准教授 (20580369)
山手 丈至 大阪府立大学, 生命環境科学研究科, 教授 (50150115)
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| Research Collaborator |
Kuramoto Takashi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | オリゴデンドロサイト / ミエリン / モデル動物 / 多発性硬化症 / 脱髄 |
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| Outline of Final Research Achievements |
Prior to the myelin destruction at 7-8 weeks, disrupted expression of Aspa mRNA and ASPA protein undergoes from early stage of myelinogenesis. The ASPA protein is localized to oligodendrocytes, suggesting that the Aspa gene serves as a marker for oligodendrocyte dysfunction. In addition, detailed pathological analysis suggested that both mutants might have oligodendrocyte differentiation, maturation and dysfunction. In dmy rats, Tribbles homolog 3 (Trib3) showed a marked increase in expression, suggesting the involvement of oxidative stress and endoplasmic reticulum stress in myelin injury in dmy rats. Pathological analysis of newly established Aspa knockout rats was carried out, and in Aspa knockout rats, edema-like changes of myelin were observed, suggesting astrocyte dysfunction and oligodendrocyte differentiation abnormalities.
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| Academic Significance and Societal Importance of the Research Achievements |
複数のミエリン疾患モデルラットの病態比較から，Aspa遺伝子の発現がオリゴデンドロサイトの機能を評価する指標として優れていること，Trib3がミエリン障害における酸化ストレスや小胞体ストレスの指標となり得ることを示した．難治性疾患のミエリン病変の病理発生を検討する上で，興味深い知見を得ることができた．
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