Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord.
Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord.
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DOI：
10.1186/1742-2094-8-158
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发表时间：
2011-11-13
影响因子：
9.3
通讯作者：
Stallcup WB
中科院分区：
文献类型：
--
作者：
Kucharova K;Chang Y;Boor A;Yong VW;Stallcup WB
多发性硬化症（MS）是一种脱髓鞘疾病，其中血液来源的免疫细胞和活化的小胶质细胞损害中枢神经系统中的髓鞘。虽然少突胶质细胞祖细胞（OPC）对于产生用于髓鞘修复的少突胶质细胞是必不可少的，但其他细胞类型也参与损伤和修复过程。NG 2蛋白聚糖由OPC、周细胞和巨噬细胞/小胶质细胞表达。在这份报告中，我们研究了NG 2对脊髓脱髓鞘/髓鞘再生过程中这些细胞类型的影响。通过将1%溶血素微量注射到腰脊髓中来产生脱髓鞘病变。脱髓鞘后，通过免疫染色研究野生型小鼠中NG 2的表达模式。还在野生型和NG 2缺失小鼠中使用免疫标记以比较髓鞘损伤的程度、髓鞘修复的动力学以及OPC、周细胞和巨噬细胞/小胶质细胞的各自响应。通过BrdU掺入研究定量细胞增殖，并使用qRT-PCR评价细胞因子表达水平。野生型小鼠脊髓脱髓鞘的初始体积是NG 2缺失小鼠的两倍。然而，在随后的5周内，野生型小鼠的髓鞘形成改善了6倍，而NG 2缺失小鼠仅改善了2倍。NG 2消融还导致三种受影响细胞类型中的每一种的数量减少。BrdU掺入研究表明，细胞增殖减少是三个关键细胞群中每一个的NG 2依赖性降低的重要因素。此外，NG 2消融减少巨噬细胞/小胶质细胞迁移，并将细胞因子表达从促炎表型转变为抗炎表型。NG 2表达的缺失导致OPC、周细胞和巨噬细胞/小胶质细胞的增殖减少，从而减少脱髓鞘脊髓病变中所有三种细胞类型的丰度。作为这些NG 2依赖性变化的结果，NG 2缺失小鼠中的脱髓鞘和髓鞘再生过程与野生型小鼠中所见的不同，NG 2缺失小鼠中髓鞘损伤和修复均减少。这些研究确定NG 2是调节髓鞘加工的重要因素，表明蛋白聚糖的治疗靶向可能提供一种操纵脱髓鞘疾病中细胞行为的方法。
Multiple sclerosis (MS) is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs) are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination. Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR. The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype. Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result of these NG2-dependent changes, the course of demyelination and remyelination in NG2 null mice differs from that seen in wild type mice, with both myelin damage and repair being reduced in the NG2 null mouse. These studies identify NG2 as an important factor in regulating myelin processing, suggesting that therapeutic targeting of the proteoglycan might offer a means of manipulating cell behavior in demyelinating diseases.
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DOI：
10.1023/a:1025751900356
发表时间：
2002-07-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Butt, AM;Kiff, J;Berry, M
通讯作者：
Berry, M
影响因子：
4.8
作者：
Goretzki, L;Burg, MA;Stallcup, WB
通讯作者：
Stallcup, WB
影响因子：
3.2
作者：
Kadoya, Kuniko;Fukushi, Jun-ichi;Stallcup, William B.
通讯作者：
Stallcup, William B.
影响因子：
3.3
作者：
Fukushi, J;Makagiansar, IT;Stallcup, WB
通讯作者：
Stallcup, WB
影响因子：
3.3
作者：
Kucharova K;Stallcup WB
通讯作者：
Stallcup WB