Lentiviral vector delivery of short hairpin RNA to NgR1 promotes nerve regeneration and locomotor recovery in injured rat spinal cord.

Lentiviral vector delivery of short hairpin RNA to NgR1 promotes nerve regeneration and locomotor recovery in injured rat spinal cord.
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慢病毒载体将短发夹 RNA 传递至 NgR1 可促进受损大鼠脊髓的神经再生和运动恢复

DOI:
10.1038/s41598-018-23751-2
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发表时间:
2018-04-03
期刊:
影响因子:
4.6
通讯作者:
Wan Y
Wan Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhao X;Peng Z;Long L;Chen N;Zheng H;Deng DYB;Wan Y

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Nogo受体1(NgR 1)是髓鞘相关抑制剂(迈斯)的高亲和力受体,并且抑制神经发生。慢病毒载体通常用于改变靶基因的表达。然而,关于携带NgR 1 shRNA的慢病毒载体(LV-NgR 1 shRNA)在脊髓损伤(SCI)后神经发生中的潜在作用,目前还知之甚少。本研究将大鼠随机分为三组:LN组(注射LV-NgR 1 shRNA)、LC组(注射LV对照组)和Sham组(仅行椎板切除术)。注射LV后8周,通过组织学检查脊髓腔大小的变化,并通过免疫组织化学检查NgR 1表达、细胞凋亡、星形胶质细胞、神经元和髓鞘形成的变化。使用Basso、Beattie和Bresnahan(BBB)运动量表评估运动功能。接受LV-NgR 1 shRNA的动物显著改善了运动功能。这些动物在治疗后8周还显示出神经纤维、突触和髓鞘形成水平的增加,病变腔和细胞凋亡水平的降低。这些发现证明NgR 1可能是SCI治疗的一个有希望的靶点。
Nogo receptor 1 (NgR1) is a high-affinity receptor of myelin-associated inhibitors (MAIs), and suppresses neurogenesis. Lentiviral vector are commonly used to alter the expression of targeted genes. However, little is known about the potential function of lentiviral vector harboring NgR1 shRNA (LV-NgR1 shRNA) on neurogenesis in spinal cord injury (SCI). In this study, the rats were randomly divided into three groups: including the LN (LV-NgR1 shRNA injection), LC (LV-control shRNA injection) and Sham (laminectomy only). Eight weeks post-injection of LV, spinal cords were examined by histology for changes in cavity size and by immunohistochemistry for changes in expression of NgR1, cell apoptosis, astrocytes, neurons and myelination. Motor function was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor scale. Animals that received LV-NgR1 shRNA remarkably improved the motor function. These animals also showed an increase in levels of nerve fibers, synapses and myelination, a decrease in levels of lesion cavity and cell apoptosis at 8 weeks post-treatment. These findings give evidence that NgR1 may be a promising target for SCI treatment.
DOI: 10.4161/cc.2.3.376
发表时间: 2003-01-01
期刊: CELL CYCLE
影响因子: 4.3
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发表时间: 2006-11-01
影响因子: 3.5
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