Characteristics of astrocytes in Fukuyama congenital muscular dystrophy.

基底膜异常导致的神经胶质细胞界限破坏被认为与福山先天性肌营养不良症(FCMD)脑损伤的发生有关。胶质细胞的界限由星形细胞终足形成，并被基底膜覆盖。我们先前报道，FCMD脑中的未成熟星形胶质细胞可能不能参与基底膜的功能。为探讨FCMD脑内星形胶质细胞的特点，对8例FCMD患者(其中2例为胎儿)大脑和延髓进行了氧化修饰终产物免疫组织化学染色。对照组为非FCMD组，其中包括3例胎儿。在胎儿病例中，FCMD组与对照组之间无显著差异。在儿童和成人病例中，晚期糖基化终产物在FCMD患者的脑星形胶质细胞中呈弱阳性，而在大多数对照病例中为阴性。其他氧化修饰内源性产物如4-羟基壬烯醛和8-羟基脱氧鸟苷，以及非氧化途径形成的终产物如吡咯啉和甲基乙醛等未见差异。MN超氧化物歧化酶阳性的星形胶质细胞在FCMD患者中有增加的趋势。我们的数据表明，FCMD中的星形胶质细胞对氧化应激敏感，而Mn-SOD对氧化应激表现出反应性增加。FCMD星形胶质细胞似乎在脑损伤的形成中起着重要作用。随着病例的增多，将进行定量分析，如蛋白质印迹杂交。

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.