Characteristics of astrocytes in Fukuyama congenital muscular dystrophy.

由于基底膜异常而导致的神经胶质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。神经胶质界限由星形胶质细胞末足形成，并被基底膜覆盖。我们之前报道过，FCMD 大脑中未成熟的星形胶质细胞可能无法参与基底膜的功能。对8例FCMD病例（包括2例胎儿病例）的大脑和延髓进行氧化修饰终产物的免疫组织化学检查，以阐明FCMD脑中星形胶质细胞的特征。非 FCMD 病例（包括 3 例胎儿病例）用作对照。在胎儿病例中，FCMD 与对照病例之间未发现显着差异。在儿童和成人病例中，FCMD 病例的脑星形胶质细胞晚期糖基化终末产物往往呈弱阳性，尽管在大多数对照病例中呈阴性。其他氧化修饰内产物如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。 FCMD 病例中锰超氧化物歧化酶阳性的星形胶质细胞呈增加趋势。我们的数据表明，FCMD 中的星形胶质细胞似乎对脑损伤的形成起着重要作用，对氧化应激敏感，并且 Mn SOD 显示出针对氧化应激的反应性增加。随着病例的积累，将进行Western blot杂交等定量分析。

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.