Characteristics of astrocytes in Fukuyama congenital muscular dystrophy.

由于基底膜异常导致的胶质界膜破坏被认为与福山先天性肌营养不良症（FCMD）的脑病变的发生有关。胶质界膜由星形胶质细胞的终足形成，并被基底膜覆盖。我们以前报道过FCMD脑中未成熟的星形胶质细胞可能无法参与基底膜的功能。为了解FCMD脑内星形胶质细胞的特点，对8例FCMD患者（包括2例胎儿）的大脑和延髓进行了氧化修饰终产物的免疫组织化学检测。非FCMD病例（包括3例胎儿病例）用作对照。胎儿期FCMD与对照组比较差异无显著性。在儿童和成人病例中，FCMD病例的脑星形胶质细胞中晚期糖基化终产物呈弱阳性，而对照组中大多数为阴性。其他氧化修饰的终产物如4-羟基壬烯醛和8-羟基脱氧鸟苷，或非氧化途径形成的终产物如吡咯啉和甲基乙二醛没有发现差异。星形胶质细胞锰超氧化物歧化酶阳性倾向于增加FCMD病例。我们的数据表明，星形胶质细胞在FCMD，这似乎发挥了重要的作用，形成的脑损伤，是敏感的氧化应激和锰超氧化物歧化酶对氧化应激反应性增加。随着病例的积累，将进行定量分析，如Western印迹杂交。

Disruption of the glia limitans due to abnormal basement membrane has been considered to be involved in the genesis of the brain lesion of Fukuyama congenital muscular dystrophy (FCMD). The glia limitans is formed by astrocytic endfeet and is covered with the basement membrane. We reported previously that immature astrocytes in the FCMD brain may not be able to participate in the function of the basement membrane. Immunohistochemical examination for oxidative modification endproducts was performed in the cerebrum and medulla oblongata of 8 FCMD cases including 2 fetal cases to elucidate the characteristics of astrocytes in the FCMD brain. Non-FCMD cases including 3 fetal cases were used for controls. In fetal cases, significant difference was not found between FCMD and control cases. In cases of children and adults, advanced glycation endproduct tended to be weakly positive in cerebral astrocytes of FCMD cases, although it was negative in most of the control cases. Difference was not found in other oxidative modification endoproducts such as 4-hydroxynonenal and 8-hydroxy deoxyguanosine, or endproducts formed by non-oxidative pathway such as pyrraline and methylglyoxal. Astrocytes positive for Mn superoxide dismutase tended to increase in FCMD cases. Our data suggest that astrocytes in FCMD, which seems to play a significant role for formation of the brain lesion, is sensitive to oxidative stress and Mn SOD shows reactive increase against oxidative stress. Quantitative analysis such as Western blot hybridization will be performed with more accumulation of cases.