• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of neuroinflammation >Dysregulation of the complement cascade in the hSOD1G93A transgenic mouse model of amyotrophic lateral sclerosis
【24h】

Dysregulation of the complement cascade in the hSOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

机译：肌萎缩性侧索硬化的hSOD1 G93A 转基因小鼠模型中补体级联的失调

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement components (C1qB, C4, factor B, C3/C3b, C5 and CD88) and regulators (CD55 and CD59a) in the lumbar spinal cord of hSOD1G93A mice during defined disease stages. Methods hSOD1G93A and wild-type mice were examined at four different ages of disease progression. mRNA and protein expression of complement components and regulators were examined using quantitative PCR, western blotting and ELISA. Localisation of complement components within lumbar spinal cord was investigated using immunohistochemistry. Statistical differences between hSOD1G93A and wild-type mice were analysed using a two-tailed t-test at each stage of disease progression. Results We found several early complement factors increased as disease progressed, whilst complement regulators decreased; suggesting overall increased complement activation through the classical or alternative pathways in hSOD1G93A mice. CD88 was also increased during disease progression, with immunolocalisation demonstrating expression on motor neurons and increasing expression on microglia surrounding the regions of motor neuron death. Conclusions These results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1G93A mouse. Hence, reducing complement-induced inflammation could be an important therapeutic strategy to treat ALS.
机译：背景技术先天性免疫补体系统的成分与肌萎缩性侧索硬化症（ALS）的发病机制有关。然而，尚未对该疾病中补体表达进行全面检查。因此，本研究旨在确定在定义的疾病阶段中，hSOD1G93A小鼠腰脊髓中补体成分（C1qB，C4，B因子，C3 / C3b，C5和CD88）和调节剂（CD55和CD59a）的表达。方法在四个不同年龄的疾病进展期检查hSOD1G93A和野生型小鼠。补体成分和调节剂的mRNA和蛋白表达使用定量PCR，蛋白质印迹和ELISA进行了检查。使用免疫组织化学研究补体成分在腰脊髓内的定位。在疾病进展的每个阶段，使用双尾t检验分析hSOD1G93A与野生型小鼠之间的统计差异。结果我们发现，随着疾病的进展，一些早期的补体因子增加，而补体调节因子则下降。提示通过hSOD1G93A小鼠的经典途径或替代途径，补体激活总体增加。 CD88在疾病进展过程中也增加，免疫定位表明在运动神经元上的表达和在运动神经元死亡区域周围的小胶质细胞上的表达增加。结论这些结果表明，hSOD1G93A小鼠中局部补体激活和CD88表达增加可能与运动神经元死亡和ALS病理有关。因此，减少补体诱导的炎症可能是治疗ALS的重要治疗策略。

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