Gene expression alterations of neurotrophins, their receptors and prohormone convertases in a rat model of spinal cord contusion
Gene expression alterations of neurotrophins, their receptors and prohormone convertases in a rat model of spinal cord contusion
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DOI：
10.1016/j.neulet.2008.06.046
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发表时间：
2008-08-29
影响因子：
2.5
通讯作者：
Tavallaei, Mahmoud
中科院分区：
文献类型：
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作者：
Hajebrahimi, Zahra;Mowla, Seyed Javad;Tavallaei, Mahmoud
我们使用半定量RT-PCR方法研究了脊髓挫伤大鼠模型中神经元存活和死亡的主要调节因子、神经营养因子（NT）、NT受体和激素原转化酶（PC）表达的变化。结果显示，早在损伤后6小时，损伤脊髓中NT家族成员（神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养因子-3 (NT-3)）的表达就明显下降。之后，表达量恢复到对照水平。此外，所有NTs高亲和力Trk受体的表达在挫伤后严重下降。TrkA和TrkC的表达分别在损伤后6和12 h完全关闭，TrkB受体的表达在损伤后12 h下降，此后一直保持在这个低水平。与Trk受体的表达模式相反，p75NTR受体在挫伤后表现出明显的上调。脊髓损伤后，参与组成性分泌通路的PC成员如furin、PACE4和PC7的表达增加，而参与调节性分泌通路的PC成员如PC1和PC2的表达减少。总之，NTs及其指定的Trk受体和PC1/PC2酶的下调以及p75NTR的上调促进了损伤后神经元的死亡。我们的研究结果表明，移植前在宿主和/或移植物细胞中过表达nt、Trk受体和PC1/PC2或干扰p75NTR的表达均可提高移植成功率。2008爱思唯尔爱尔兰有限公司阿里版权所有。
We have used a semi-quantitative RT-PCR approach to investigate the alterations in the expression of the main regulators of neuronal survival and death, neurotrophins (NTs), NT receptors, and prohormone convertases (PC), in a rat model of spinal cord contusion. Our results revealed that the expression of the members of NT family (Nerve-Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Neurotrophin-3 (NT-3)) is significantly declined in the injured spinal cord, as early as 6 h after the induction of the contusion. The expression was recovered afterward to that of the control levels. Furthermore, the expression of all NTs high-affinity Trk receptors decreased severely after the contusion. While the expression of TrkA and TrkC were completely shut down after 6 and 12 h after injury respectively, the expression of TrkB receptor declined at 12 h after injury and remained at this low level thereafter. In contrast to the pattern of Trk receptor expression, p75NTR receptor showed a significant upregulation after contusion. The expression of PC members functioning in the constitutive secretory pathway, i.e. furin, PACE4 and PC7, increased after damage, while the expression of PC members acting in regulated secretory pathway, PC1 and PC2, reduced after spinal cord injury. All together, the down-regulation of NTs, their designated Trk receptors and PC1/PC2 enzymes along with an upregulation of p75NTR promote neuronal death after injury. Our results suggest that either overexpression of NTs, Trk receptors and PC1/PC2 or interfering with the expression of p75NTR in host and/or grafted cells before transplantation could increase the success of the transplantation. (c) 2008 Elsevier Ireland Ltd. Ali rights reserved.