Cyclin D1 is required for proliferation of olig2-expressing progenitor cells in the injured cerebral cortex
Cyclin D1 is required for proliferation of olig2-expressing progenitor cells in the injured cerebral cortex
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DOI：
10.1002/glia.22533
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发表时间：
2013-09-01
期刊：
影响因子：
6.2
通讯作者：
Atanasoski, Suzana
中科院分区：
文献类型：
--
作者：
Nobs, Lionel;Nestel, Sigrun;Atanasoski, Suzana
对中枢神经系统损伤后神经胶质细胞增殖的分子机制知之甚少。为了验证G1调节细胞周期蛋白D1对损伤诱导的神经胶质细胞分裂至关重要的假设，我们应用了一个损伤模型，该模型在一个明确定义的区域内引起脑损伤。为此，我们将神经毒素鹅膏蕈氨酸注射到成年小鼠的前额叶皮层中，这会导致局部神经细胞损失，但不会影响神经胶质细胞的存活。在这里，我们表明，细胞周期蛋白D1免疫反应性神经毒素注射后急剧增加。我们发现，细胞周期蛋白D1-免疫阳性（细胞周期蛋白D1+）细胞群内的病变区域组成的Olig2+少突胶质细胞祖细胞在很大程度上。对细胞周期蛋白D1缺陷小鼠的分析表明，Olig2+细胞的增殖率在细胞周期蛋白D1缺失时降低。此外，我们表明，细胞周期蛋白依赖性激酶（cdk）4，而不是cdk6或cdk2，是必不可少的驱动寡核苷酸2表达细胞在我们的损伤模型中的细胞分裂。这些数据表明，不同的细胞周期蛋白调节寡聚体2+祖细胞的增殖后，中枢神经系统损伤。
Little is known about the molecular mechanisms driving proliferation of glial cells after an insult to the central nervous system (CNS). To test the hypothesis that the G1 regulator cyclin D1 is critical for injury-induced cell division of glial cells, we applied an injury model that causes brain damage within a well-defined region. For this, we injected the neurotoxin ibotenic acid into the prefrontal cortex of adult mice, which leads to a local nerve cell loss but does not affect the survival of glial cells. Here, we show that cyclin D1 immunoreativity increases drastically after neurotoxin injection. We find that the cyclin D1-immunopositive (cyclin D1+) cell population within the lesioned area consists to a large extent of Olig2+ oligodendrocyte progenitor cells. Analysis of cyclin D1-deficient mice demonstrates that the proliferation rate of Olig2+ cells diminishes upon loss of cyclin D1. Further, we show that cyclin-dependent kinase (cdk) 4, but not cdk6 or cdk2, is essential for driving cell division of Olig2-expressing cells in our injury model. These data suggest that distinct cell cycle proteins regulate proliferation of Olig2+ progenitor cells following a CNS insult.