The Pathogenesis of Demyelination in Krabbe's disease and it's therapy

我们采用Twitcher小鼠和Niemann-Pick小鼠模型研究Krabbe病脱髓鞘的发病机制。在抽搐小鼠背根神经节中发现了明显的精神素积累。精神素在弗洛氏细胞白质营养不良的脱髓鞘中起重要作用。精神碱抑制h -半乳糖向培养的胶质细胞中脑苷和硫脂的掺入。结果表明，精神科苷参与了体外脱髓鞘的形成。精神碱处理的细胞显示出细胞骨架的破坏，表明精神碱可能通过抑制氧化磷酸化影响线粒体功能。对氨基苯基- α -甘露糖苷制备的脂质体通过血脑屏障被充分地纳入小鼠大脑。提示神经胶质细胞可识别膜表面的甘露糖分子。发现外源性胆固醇酯化在Niemann-Pick小鼠成纤维细胞中存在。胆固醇酯化受损可能是Niemann-Pick模型小鼠发病的重要机制。

We investigated the pathogenesis of demyelination in Krabbe's disease using Twitcher mouse and the cholesterol metabolism in Niemann-Pick mouse model.1. Marked accumulation of psychosine was found in the Twitcher mouse Dorsal Root Ganglion. And psychosine played an important role for the demyelination in Floboid Cell Leukodystrophy.2. Psychosine inhibited the incorporation of H-galactose into cerebroside and sulfatide in cultured colgodendroglia. This results suggested that psycgosine participate in the demyelination in vitro.3. Psychosine treated cells showed destruction of cytoskeleton and suggested that psychosine influences mitochondrial function, possibly through the inhibition of oxidative phosphorylation.4. Liposomes prepared from p-aminophenyl-alpha-mannoside were sufficiently incorporated into the mouse brain across the blood brain barrier. It was suggested that glial cell recognize mannose molecude on the surface of the membrane.5. It was found that the exogenous cholesterol esterification was found in Niemann-Pick mouse fibroblasts. The impaired cholesterol esterification might be an important role for the pathogenesis of Niemann-Pick mouse model.