Formation of compact myelin is required for maturation of the axonal cytoskeleton
Formation of compact myelin is required for maturation of the axonal cytoskeleton
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DOI：
10.1523/jneurosci.19-17-07278.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Lee, VMY
中科院分区：
文献类型：
--
作者：
Brady, ST;Witt, AS;Lee, VMY
虽然传统的作用归因于髓鞘神经胶质细胞的结构和支持，致密的髓鞘神经系统的正常功能的重要性可以推断从髓鞘蛋白质和神经病理学与髓鞘丢失相关的突变。已知髓鞘形成施旺细胞影响外周轴突的局部性质（de Waegh等人，1992），但是关于少突胶质细胞对CNS轴突的作用知之甚少。颤抖突变小鼠的髓鞘碱性蛋白基因缺失，消除了CNS中的致密髓鞘。在颤抖的小鼠中，局部轴突特征如细胞骨架蛋白的磷酸化和神经元核周功能如细胞骨架基因表达都被改变。这导致的变化，在shiverer无髓轴突的轴突细胞骨架的组织和组成相对于年龄匹配的野生型有髓纤维，虽然连接和神经元活动的模式是可比的。值得注意的是，具有薄髓鞘的转基因shiverer小鼠显示中间表型，表明CNS神经元对髓鞘厚度敏感。这些结果表明，在大的中枢神经系统神经元中，神经元细胞骨架的正常成熟需要形成正常致密的髓鞘。
Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.