Cellular responses in the spinal cord during development of hypomyelination in the mv rat
Cellular responses in the spinal cord during development of hypomyelination in the mv rat
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DOI：
10.1016/j.brainres.2007.12.022
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发表时间：
2008-02-01
期刊：
影响因子：
2.9
通讯作者：
Kuwamura, Mitsuru
中科院分区：
文献类型：
--
作者：
Izawa, Takeshi;Takenaka, Shigeo;Kuwamura, Mitsuru
髓鞘空泡化（myelin vacuolization，mv）大鼠是一种常染色体隐性遗传突变体，其特征是在整个中枢神经系统（CNS）的髓鞘中形成低髓鞘化和空泡。先前的遗传学研究揭示了mu突变大鼠的attractin基因的无效突变。已经知道吸引素位点的突变导致髓鞘改变，但其详细的发病机制仍不清楚。在这项研究中，我们检测了2、4、6和8周龄mv大鼠脊髓中胶质细胞的变化，并鉴定了大鼠脊髓中表达吸引素的细胞。尽管髓鞘紊乱的严重程度和范围随着年龄的增长而增加，但在任何年龄的mv大鼠中，少突胶质细胞的数量和形态都没有发现异常。与髓鞘异常同时，从2周开始出现进行性星形胶质细胞增生。从第6周开始，在mv大鼠的灰质中观察到明显的小胶质细胞活化，与严重的髓鞘破坏一致。双标记研究表明，表达吸引素的细胞主要是野生型大鼠脊髓白色物质中的少突胶质细胞，而在mu大鼠中未检测到吸引素阳性细胞。以往的研究表明，Luxol固蓝染色模式和髓鞘碱性蛋白的免疫反应性在mu大鼠减少。因此，本研究表明，mv大鼠中吸引素缺陷导致少突胶质细胞功能障碍，并与星形胶质细胞增生和小胶质细胞活化有关。这些数据表明，吸引素可能直接参与中枢神经系统髓鞘形成的少突胶质细胞的功能。(c)2008 Elsevier B.V.保留所有权利。
The myelin vacuolation (mv) rat is an autosomal recessive mutant characterized by hypomyelination and vacuole formation in the myelin throughout the central nervous system (CNS). Previous genetic studies have revealed a null mutation in attractin gene of the mu mutant rat. It has been known that mutation at the attractin locus results in myelin alterations, but their detailed pathogenesis is still unclear. In this study, we examined glial changes in the spinal cord of mv rats at 2, 4, 6, and 8 weeks of age and identified attractin-expressing cells in the rat spinal cord. No abnormality was found in the number and morphology of oligodendrocytes in mv rats at any of the ages examined, although the severity and extent of myelin disorder increased with age. Coincident with the myelin abnormalities, there was progressive astrogliosis from 2 weeks. Marked microglial activation was observed exclusively in the gray matter of mv rats from 6 weeks, coincident with severe myelin disruption. A double-labeling study demonstrated that attractin-expressing cells are mostly oligodendrocytes in the white matter of the spinal cord of wild-type rats, whereas no attractin-positive cells were detected in mu rats. Previous study demonstrated that Luxol fast blue staining pattern and immunoreactivity for myelin basic protein were decreased in mu rats. Therefore, this study indicates that the attractin defect results in oligodendrocyte dysfunction, and is associated with astrogliosis and microglial activation in mv rats. The data suggest that attractin may be directly involved in the function of oligodendrocytes in CNS myelination. (c) 2008 Elsevier B.V. All rights reserved.