Coetzee T, Dupree J L, Popko B
Neuroscience Center, University of North Carolina at Chapel Hill, 27599-7250, USA.
J Neurosci Res. 1998 Dec 1;54(5):613-22. doi: 10.1002/(SICI)1097-4547(19981201)54:5<613::AID-JNR6>3.0.CO;2-V.
Vertebrate myelin is enriched in the lipid galactocerebroside (GalC) and its sulfated derivated sulfatide. To understand the in vivo function of these lipids, we analyzed myelination in mice that contain a null mutation in the gene encoding UDP-galactose:ceramide galactosyltransferase, the enzyme responsible for catalyzing the final step in GalC synthesis. Galactolipid-deficient myelin is regionally unstable and progressively degenerates. At postnatal day 30, demyelination is restricted to the midbrain and hindbrain, but by postnatal day 90, it spreads throughout the central nervous system. Activated microglial cells and reactive astrocytes appear with the loss of myelin in older animals. Nonetheless, major myelin protein gene mRNA levels are normal throughout the life of these animals, suggesting that widespread oligodendrocyte death is not the primary cause of demyelination. The developmental switch in myelin-associated glycoprotein isoform expression, however, does not occur normally in these mice, suggesting an alteration in oligodendrocyte maturation. Taken together, these findings indicate that GalC and sulfatide are required for the long-term maintenance of myelin and that their absence may have subtle effects on the development of oligodendrocytes.
脊椎动物的髓磷脂富含脂质半乳糖脑苷脂（GalC）及其硫酸化衍生物硫苷脂。为了解这些脂质在体内的功能，我们分析了编码UDP-半乳糖：神经酰胺半乳糖基转移酶（该酶负责催化GalC合成的最后一步）的基因发生无效突变的小鼠的髓鞘形成情况。缺乏半乳糖脂的髓磷脂在区域上不稳定并逐渐退化。在出生后第30天，脱髓鞘仅限于中脑和后脑，但到出生后第90天，它会扩散到整个中枢神经系统。在年龄较大的动物中，活化的小胶质细胞和反应性星形胶质细胞随着髓磷脂的丧失而出现。尽管如此，在这些动物的整个生命过程中，主要髓磷脂蛋白基因的mRNA水平是正常的，这表明广泛的少突胶质细胞死亡不是脱髓鞘的主要原因。然而，在这些小鼠中，髓鞘相关糖蛋白异构体表达的发育转换并未正常发生，这表明少突胶质细胞成熟存在改变。综上所述，这些发现表明GalC和硫苷脂是髓磷脂长期维持所必需的，并且它们的缺失可能对少突胶质细胞的发育有微妙影响。
