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

我们利用Twitcher小鼠研究了Krabbe病脱髓鞘的发病机制，并在Niemann-Pick小鼠模型中研究了胆固醇代谢。抽动小鼠背根神经节内有明显的精神素积聚。结论：1.精神病素在Floboid细胞白质营养不良脱髓鞘中起重要作用。心得安可抑制H-半乳糖掺入培养的大鼠神经胶质细胞的脑苷脂和硫脂中。这一结果提示心得安参与了体外脱髓鞘的过程。精神药物处理的细胞显示出细胞骨架的破坏，提示精神药物可能通过抑制氧化磷酸化影响线粒体的功能。由对氨基苯基-α-甘露糖苷制备的脂质体通过血脑屏障充分进入小鼠脑内。提示神经胶质细胞识别膜表面的甘露糖分子。结果发现，在Niemann-Pick小鼠成纤维细胞中存在外源性胆固醇的酯化。胆固醇酯化障碍可能是Niemann-Pick小鼠模型发病的重要原因之一。

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.