Alterations in the oligodendrocyte lineage, myelin, and white matter in adult mice lacking the chemokine receptor CXCR2
Alterations in the oligodendrocyte lineage, myelin, and white matter in adult mice lacking the chemokine receptor CXCR2
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DOI：
10.1002/glia.20383
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发表时间：
2006-10-01
期刊：
影响因子：
6.2
通讯作者：
Miller, Robert H.
中科院分区：
文献类型：
--
作者：
Padovani-Claudio, Dolly A.;Liu, Liping;Miller, Robert H.
少突胶质细胞前体细胞 (OPC) 的增殖和迁移对于中枢神经系统 (CNS) 髓磷脂的发育至关重要。先前的研究表明，趋化因子CXCL1的局部表达通过受体CXCR2发出信号，抑制脊髓OPC在发育过程中的迁移并增强其增殖。在这里，我们报告了 Cxcr2(-/-) 小鼠成年中枢神经系统的结构和功能改变。在Cxcr2(-/-)成年小鼠中，我们观察到Cxcr2(-/-)成年小鼠少突胶质细胞谱系细胞密度的区域性改变，皮质和前连合减少，但胼胝体和脊髓增加。在 Cxcr2(-/-) 成年小鼠中也观察到脊髓 NG2 阳性细胞的密度和树状化增加。与野生型（WT）同窝小鼠相比，Cxcr2（-/-）小鼠脊髓白质面积显着减少，髓鞘厚度减少，脊髓诱发电位中枢传导速率减慢，但轴突口径或数量没有显着变化。生化分析显示髓鞘碱性蛋白（MBP）、蛋白脂质蛋白（PLP）和胶质纤维酸性蛋白（GFAP）水平降低。体外研究表明，Cxcr2(-/-) 脊髓培养物中分化的少突胶质细胞数量减少。总之，这些发现表明趋化因子受体 CXCR2 对于脊椎动物中枢神经系统中少突胶质细胞谱系、髓鞘形成和白质的发育和维持非常重要。 (c) 2006 Wiley-Liss, Inc.
Oligodendrocyte precursor cell (OPC) proliferation and migration are critical for the development of myelin in the central nervous system (CNS). Previous studies showed that localized expression of the chemokine CXCL1 signals through the receptor CXCR2 to inhibit the migration and enhance the proliferation of spinal cord OPCs during development. Here, we report structural and functional alterations in the adult CNS of Cxcr2(-/-) mice. In Cxcr2(-/-) adult mice, we observed regional alterations in the density of oligodendrocyte lineage cells in Cxcr2(-/-) adult mice, with decreases in the cortex and anterior commissure but increases in the corpus callosum and spinal cord. An increase in the density and arborization of spinal cord NG2 positive cells was also observed in Cxcr2(-/-) adult mice. Compared with wild-type (WT) littermates, Cxcr2(-/-) mice exhibited a significant decrease in spinal cord white matter area, reduced thickness of myelin sheaths, and a slowing in the rate of central conduction of spinally elicited evoked potentials without significant changes in axonal caliber or number. Biochemical analyses showed decreased levels of myelin basic protein (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP). In vitro studies showed reduced numbers of differentiated oligodendrocytes in Cxcr2(-/-) spinal cord cultures. Together, these findings indicate that the chemokine receptor CXCR2 is important for the development and maintenance of the oligodendrocyte lineage, myelination, and white matter in the vertebrate CNS. (c) 2006 Wiley-Liss, Inc.