Sulfatide is essential for the maintenance of CNS myelin and axon structure
Sulfatide is essential for the maintenance of CNS myelin and axon structure
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DOI：
10.1002/glia.20292
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发表时间：
2006-03-01
期刊：
影响因子：
6.2
通讯作者：
Dupree, JL
中科院分区：
文献类型：
--
作者：
Marcus, J;Honigbaum, S;Dupree, JL
半乳糖脑苷（Ga1C）和硫脂是丰富的髓磷脂脂。在不能合成这些脂质的小鼠中，髓磷脂变薄，局部不稳定，并表现出一些微妙的结构异常。虽然半乳糖脂缺失小鼠在半乳糖脂功能分析中是有益的，但不可能单独区分半乳糖脂c和硫脂的功能。在目前的工作中，我们分析了形成正常水平的Ga1C但不能合成硫脂的小鼠模型。通过比较无半乳糖脂和无硫脂小鼠之间的大量形态学特征，我们已经开始区分这些密切相关的脂质的特定功能。这两种突变体之间最显著的区别是，与无半乳糖脂的动物相比，无硫脂的年轻成年小鼠的髓磷脂发育异常（例如，髓磷脂鞘冗余和松散）减少。尽管硫脂在髓磷脂发育中发挥的作用有限，但这种脂质对于髓磷脂的维持是必不可少的，因为与同窝野生型小鼠相比，在无硫脂小鼠中，髓鞘冗余、不紧致和退化的患病率以及淋巴结/副淋巴结结构的恶化显著增加。最后，我们发现硫脂脂在中枢神经系统维持中的作用并不局限于髓鞘，因为在年轻的成年突变小鼠中轴突的直径和圆度是正常的，但在没有硫脂脂的老年动物中却发生了显著改变。(c) 2005 Wiley-Liss, Inc。
Galactocerebroside (Ga1C) and sulfatide are abundant myelin lipids. In mice incapable of synthesizing these lipids, myelin is thin and regionally unstable and exhibits several subtle structural abnormalities. Although galactolipid-null mice have been beneficial in the analysis of galactolipid function, it has not been possible to differentiate between the functions of GalC and sulfatide with these mice alone. In the present work, we have analyzed a murine model that forms normal levels of Ga1C but is incapable of synthesizing sulfatide. By comparing a plethora of morphological features between the galactolipid-null and the sulfatide-null mice, we have begun to differentiate between the specific functions of these closely related lipids. The most striking difference between these two mutants is the reduction of myelin developmental abnormalities (e.g., redundant and uncompacted myelin sheaths) in young adult sulfatide-null mice as compared with the galactolipid-null animals. Although sulfatide appears to play a limited role in myelin development, this lipid is essential for myelin maintenance, as the prevalence of redundant, uncompacted, and degenerating myelin sheaths as well as deteriorating nodal/paranodal structure is increased significantly in aged sulfatide-null mice as compared with litter-mate wildtype mice. Finally, we show that the role played by sulfatide in CNS maintenance is not limited to the myelin sheath, as axonal caliber and circularity are normal in young adult mutant mice but are significantly altered in aged sulfatide-null animals. (c) 2005 Wiley-Liss, Inc.