Bosio A, Büssow H, Adam J, Stoffel W
Molecular Neuroscience Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Cologne, Joseph-Stelzmann-Strasse 52, D-50931 Cologne, Germany.
Cell Tissue Res. 1998 May;292(2):199-210. doi: 10.1007/s004410051051.
The myelin of central and peripheral nervous system of UDP-galactose-ceramide galactosyltransferase deficient mice (cgt-/-) is completely depleted of its major lipid constituents, galactocerebrosides and sulfatides. The deficiency of these glycolipids affects the biophysical properties of the myelin sheath and causes the loss of the rapid saltatory conduction velocity of myelinated axons. With the onset of myelination, null mutant cgt-/- mice develop fatal neurological defects. CNS and PNS analysis of cgt-/- mice revealed (1) hypomyelination of axons of the spinal cord and optic nerves, but no apoptosis of oligodendrocytes, (2) redundant myelin in younger mice leading to vacuolated nerve fibers in cgt-/- mice, (3) the occurrence of multiple myelinated CNS axons, and (4) severely distorted lateral loops in CNS paranodes. The loss of saltatory conduction is not associated with a randomization of voltage-gated sodium channels in the axolemma of PNS fibers. We conclude that cerebrosides (GalC) and sulfatides (sGalC) play a major role in CNS axono-glial interaction. A close axono-glial contact is not a prerequisite for the spiraling and compaction process of myelin. Axonal sodium channels remain clustered at the nodes of Ranvier independent of the change in the physical properties of myelin membrane devoid of galactosphingolipids. Increased intracellular concentrations of free ceramides do not trigger apoptosis of oligodendrocytes.
UDP-半乳糖-神经酰胺半乳糖基转移酶缺陷小鼠（cgt-/-）中枢和外周神经系统的髓磷脂完全缺乏其主要脂质成分，即半乳糖脑苷脂和硫脂。这些糖脂的缺乏影响了髓鞘的生物物理特性，并导致有髓轴突快速跳跃传导速度的丧失。随着髓鞘形成的开始，纯合突变的cgt-/-小鼠出现致命的神经缺陷。对cgt-/-小鼠的中枢神经系统和外周神经系统分析显示：（1）脊髓和视神经轴突髓鞘形成不足，但少突胶质细胞无凋亡；（2）幼年小鼠存在多余的髓磷脂，导致cgt-/-小鼠神经纤维出现空泡；（3）中枢神经系统出现多条有髓轴突；（4）中枢神经系统结旁区的侧环严重扭曲。跳跃传导的丧失与外周神经纤维轴膜中电压门控钠通道的随机化无关。我们得出结论，脑苷脂（GalC）和硫脂（sGalC）在中枢神经系统轴突-神经胶质相互作用中起主要作用。紧密的轴突-神经胶质接触不是髓鞘螺旋化和压实过程的先决条件。轴突钠通道在郎飞结处保持聚集状态，与缺乏半乳糖鞘脂的髓鞘膜物理性质变化无关。细胞内游离神经酰胺浓度的增加不会触发少突胶质细胞的凋亡。
