Pathological studies on new functions of glial cells for the development and maintenance of myelin

胶质细胞发育和维持髓磷脂新功能的病理学研究

• 批准号: 20580341
• 负责人: KUWAMURA Mitsuru
• 金额: $ 3.08万
• 依托单位: Osaka Prefecture University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20580341/
• 关键词: 脱髄; ミエリン; ミクログリア; オリゴデンドログリア; サイトカイン; グリア細胞; ミエリン形成; アトラクチン; モデル動物

The dmy rat is an autosomal recessive mutant that exhibits severe myelin destruction. The number of oligodendrocytes decreases rapidly from 7weeks of age in the dmy rat. Hypertrophic oligodendrocytes were frequently observed, and the cytoplasm was found to be intensely positive for mitochondrial markers.We found that a G-to-A transition, 177 bp downstream of exon 3 of the Mrs2 (MRS2 magnesium homeostasis factor (Saccharomyces cerevisiae)) gene.We demonstrated an abnormal iron deposition, and significant upregulation of antioxidant enzyme heme oxygenase-1 (HO-1) and iron storage protein ferritin in the dmy rat.Immunohistochemical and Western blot analyses demonstrated a considerable reduction in the expression of major CNS myelin proteins both in the white and gray matter of mv rats. However, there was no significant difference between control and mv rats in the cell number of PLP mRNA-positive oligodendrocytes either in the white or gray matter.

Dmy鼠是一种常染色体隐性遗传突变，表现出严重的髓鞘破坏。Dmy大鼠少突胶质细胞数量从7周龄开始迅速减少。在mrs2(酿酒酵母)基因外显子3下游177个碱基的G-A转换中，发现MRS大鼠脑内铁沉积异常，抗氧化酶HO-1和铁储存蛋白铁蛋白表达显著上调。免疫组织化学和免疫印迹分析显示，MV大鼠大脑白质和灰质中主要的中枢神经系统髓鞘蛋白的表达均显著降低。而对照组和MV组大鼠大脑白质和灰质中PLP mRNA阳性的少突胶质细胞的细胞数无显著差异。

项目成果

Cellular responses in the spinal cord during development of hypomyelination in the mv rat

• DOI: 10.1016/j.brainres.2007.12.022
• 发表时间: 2008-02-01
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Izawa, Takeshi;Takenaka, Shigeo;Kuwamura, Mitsuru
• 通讯作者: Kuwamura, Mitsuru

Oligodendroglial pathology in the development of myelin breakdown in the dmy mutant rat

• DOI: 10.1016/j.brainres.2011.03.009
• 发表时间: 2011-05-10
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Kuwamura, Mitsuru;Inumaki, Kazuo;Serikawa, Tadao
• 通讯作者: Serikawa, Tadao

Abnormal iron accumulation is involved in the pathogenesis of the demyelinating dmy rat but not in the hypomyelinating mv rat.

铁积累异常与脱髓鞘 dmy 大鼠的发病机制有关，但与低髓鞘 mv 大鼠的发病机制无关。

• 发表时间: 2010
• 期刊: Brain Res. 1349
• 作者: Izawa T;Yamate J;Franklin RJ;Kuwamura M.
• 通讯作者: Kuwamura M.

ミエリン異常ミュータントVFの病態解析

髓鞘异常突变体VF的病理分析

• 发表时间: 2009
• 作者: 相馬克実;他
• 通讯作者: 他

Late onset cerebellar cortical degeneration in a koala.

考拉迟发性小脑皮质变性。

• 发表时间: 2009
• 期刊: Aust Vet J. 87
• 作者: Kuwamura M;Murai F;Nishioka S;Aoki M;Ohashi F;Yamate J;Kotani T;Summers BA.
• 通讯作者: Summers BA.