...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Genes, brain, and behavior >A single intramuscular injection of rAAV-mediated mutant erythropoietin protects against MPTP-induced parkinsonism.
【24h】

A single intramuscular injection of rAAV-mediated mutant erythropoietin protects against MPTP-induced parkinsonism.

机译：一次肌肉内注射rAAV介导的突变型促红细胞生成素可预防MPTP诱发的帕金森病。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

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

摘要

Erythropoietin (Epo) is neuroprotective in a number of preparations, but can lead to unacceptably high and even lethal hematocrit levels. Recent reports show that modified Epo variants confer neuroprotection in models of glaucoma and retinal degeneration without raising hematocrit. In this study, neuroprotective effects of two Epo variants (EpoR76E and EpoS71E) were assessed in a model of Parkinson's disease. The constructs were packaged in recombinant adeno-associated viral (rAAV) vectors and injected intramuscularly. After 3 weeks, mice received five daily injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and were killed 5 weeks later. The MPTP-lesioned mice pretreated with rAAV.eGFP (negative control) exhibited a 7- to 9-Hz tremor and slower latencies to move on a grid test (akinesia). Both of these symptomatic features were absent in mice pretreated with either modified Epo construct. The rAAV.eGFP-treated mice lesioned with MPTP exhibited a 41% reduction in tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rAAV.EpoS71E construct did not protect nigral neurons, but neuronal loss in mice pretreated with rAAV.EpoR76E was only half that of rAAV.eGFP controls. Although dopamine levels were normal in all groups, 3,4-dihydroxyphenylacetic acid (DOPAC) was significantly reduced only in MPTP-lesioned mice pretreated with rAAV.eGFP, indicating reduced dopamine turnover. Analysis of TH-positive fibers in the striatum showed normalized density in MPTP-lesioned mice pretreated with rAAV.EpoS71E, suggesting that enhanced sprouting induced by EpoS71E may have been responsible for normal behavior and dopaminergic tone in these mice. These results show that systemically administered rAAV-generated non-erythropoietic Epo may protect against MPTP-induced parkinsonism by a combination of neuroprotection and enhanced axonal sprouting.
机译：促红细胞生成素（Epo）在许多制剂中都具有神经保护作用，但可能导致无法接受的高甚至致命的血细胞比容水平。最近的报告显示，修饰的Epo变体可在青光眼和视网膜变性模型中赋予神经保护作用而不会增加血细胞比容。在这项研究中，在帕金森氏病模型中评估了两种Epo变体（EpoR76E和EpoS71E）的神经保护作用。将构建体包装在重组腺相关病毒（rAAV）载体中，并肌肉注射。 3周后，小鼠每天接受五次1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）注射，并于5周后被杀死。用rAAV.eGFP预处理的MPTP病变小鼠表现出7至9 Hz的震颤，并且在网格测试中表现出较慢的潜伏期（运动障碍）。在用任一修饰的Epo构建体预处理的小鼠中都没有这两种症状。受MPA损伤的rAAV.eGFP处理的小鼠黑质中酪氨酸羟化酶（TH）阳性神经元减少41％。 rAAV.EpoS71E构建体不能保护黑色素神经元，但是用rAAV.EpoR76E预处理的小鼠的神经元丢失仅是rAAV.eGFP对照的一半。尽管多巴胺水平在所有组中都是正常的，但仅在用rAAV.eGFP预处理的MPTP病变小鼠中3,4-二羟基苯乙酸（DOPAC）显着降低，表明多巴胺周转率降低。对纹状体中TH阳性纤维的分析显示，用rAAV.EpoS71E预处理的MPTP损伤小鼠中的密度正常化，表明EpoS71E诱导的发芽增强可能是这些小鼠的正常行为和多巴胺能音调的原因。这些结果表明，通过神经保护和增强的轴突发芽相结合，全身给药的rAAV生成的非促红细胞生成素可能会预防MPTP诱导的帕金森氏病。

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