Analyses of new relationship between myelin and neurons for elucidaion of myelin degenerative disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H04595
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Osaka Prefecture University
• Principal Investigator: Kuwamura Mitsuru 大阪府立大学, 生命環境科学研究科, 准教授 (20244668)
• 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)
• Research Collaborator: Kuramoto Takashi
• Project Period (FY): 2015-04-01 – 2019-03-31
• 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

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.

Free Research Field

獣医病理学

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．