• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB.
【24h】

Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB.

机译：粘多糖贮积酶I和IIIB小鼠模型皮层中的活化小胶质细胞。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

alpha-N-Acetylglucosaminidase deficiency (mucopolysaccharidosis IIIB, MPS IIIB) and alpha-l-iduronidase deficiency (MPS I) are heritable lysosomal storage diseases; neurodegeneration is prominent in MPS IIIB and in severe cases of MPS I. We have obtained morphologic and molecular evidence for the involvement of microglia in brain pathology of mouse models of the two diseases. In the cortex, a subset of microglia (sometimes perineuronal) consists of cells that are probably phagocytic; they have large storage vacuoles, react with MOMA-2 (monoclonal antibody against macrophages) and Griffonia simplicifolia isolectin IB(4), and stain intensely for the lysosomal proteins Lamp-1, Lamp-2, and cathepsin D as well as for G(M3) ganglioside. MOMA-2-positive cells appear at 1 and 6 months in MPS IIIB and MPS I mice, respectively, but though their number increases with age, they remain sparse. However, a profusion of cells carrying the macrophage CD68macrosialin antigen appear in the cortex of both mouse models at 1 month. mRNA encoding CD68macrosialin also increases at that time, as shown by microarray and Northern blot analyses. Ten other transcripts elevated in both mouse models are associated with macrophage functions, including complement C4, the three subunits of complement C1q, lysozyme M, cathepsins S and Z, cytochrome b558 small subunit, macrophage-specific protein 1, and DAP12. An increase in IFN-gamma and IFN-gamma receptor was observed by immunohistochemistry. These functional increases may represent activation of resident microglia, an influx and activation of blood monocytes, or both. They show an inflammatory component of brain disease in the two MPS, as is known for many neurodegenerative disorders.
机译：α-N-乙酰氨基葡糖苷酶缺乏症（粘多糖贮积症IIIB，MPS IIIB）和α-1-醛糖苷酸酶缺乏症（MPS I）是可遗传的溶酶体贮积病；神经变性在MPS IIIB和MPS I的严重病例中很突出。我们已经获得了小胶质细胞参与这两种疾病的小鼠模型的脑病理学的形态学和分子学证据。在皮层中，小胶质细胞的一个子集（有时为神经胶质神经元）由可能吞噬的细胞组成。它们具有较大的储存液泡，可与MOMA-2（抗巨噬细胞的单克隆抗体）和Griffonia simplicifolia isolectin IB（4）反应，并对溶酶体蛋白Lamp-1，Lamp-2和组织蛋白酶D以及G（ M3）神经节苷脂。 MOMA-2阳性细胞分别出现在MPS IIIB和MPS I小鼠的第1和6个月，但是尽管它们的数目随着年龄的增长而增加，但仍然很少。但是，两个小鼠模型在1个月时，皮质巨噬细胞中都携带有巨噬细胞CD68macrosialin抗原。如微阵列和Northern印迹分析所示，那时编码CD68macrosialin的mRNA也增加。在这两种小鼠模型中升高的其他十个转录本均与巨噬细胞功能有关，包括补体C4，补体C1q的三个亚基，溶菌酶M，组织蛋白酶S和Z，细胞色素b558小亚基，巨噬细胞特异性蛋白1和DAP12。通过免疫组织化学观察到IFN-γ和IFN-γ受体的增加。这些功能的增强可能代表常驻小胶质细胞的激活，血液单核细胞的流入和激活或两者。它们在两种MPS中显示出脑部疾病的炎症成分，这是许多神经退行性疾病众所周知的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号