Amelioration of spinal cord injury by the regulation of neurotmphin receptor p75-mediated signaling

通过调节神经营养素受体 p75 介导的信号传导改善脊髓损伤

基本信息

批准号：
18390420
负责人：
FURUKAWA Shoei
金额：
$ 10.02万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390420/
关键词：
p75NTR neurotronhin recentor spinal cord injury apoptosis genetically modified animal recovery of locomotion activity nerve growth factor brain-derived neurotrophic factor p75^<NTR>軸索再生プロNGF ソーチリン DNAアレイ解析

项目摘要

1. Analysis of alteration of gene expression after spinal cord injuryGenes of which expression were altered in the injured spinal cord were analyzed by the DNA array method. The 46 genes including inflammatory cytokines or lymphokines were upregulated and 18 genes involving ion transporter or amino acid transporter were downregulated. We focused on and analyzed some genes related to p75NTR signaling.2 Evaluation of the peptides that suppress the p75NTR-induced negative signals.a) A peptide expected to inhibit the binding between RhoGDI and p75, and b) the peptide expected to inhibit the binding between sortilin and pro-brain-derived neurotrophic factor (BDNF) were examined their activities on the locomotion activity after spinal cord injury. However, both peptides failed to improve the locomotion activity. Various proteases induced in the injury site of the spinal cord may be responsible for the degradation of the peptides.3 Amelioration of the spinal cord injury in p75NTR gene-modifie … More d animalsThe improvement of locomotion activity after spinal cord injury was compared between p75NTR gene-disrupted mouse (KO mouse) and wild mouse. KO mouse gave higher scores of the locomotion activity than wild mouse for the first 8 days, but the difference was disappeared thereinafter, suggesting that p75NTR signal disturbs the restoration at early stages of the damage.4 Development of the conditional p75NTR transgenic (Tg) mouseThe vector DNA containing a stop codon between loxp genes and the p75NTR gene in the down stream was constructed, and transferred to fertilized eggs. Because the introduced p75NTR gene does not express as long as stop codon between loxp is not deleted, the maintenance of the animal is easy. If the transgenic mice expressing cre enzyme gene in a region-specicic manner were hybridized with this p75NTR Tg mouse, the p75NTR gene would express simultaneously in the cre enzyme expressing regions. This Tg animals would become useful tool to investigate p75NTR function in the future. Less

1.脊髓损伤后基因表达变化分析通过DNA阵列法分析损伤脊髓中表达变化的基因，包括炎症细胞因子或淋巴因子在内的46个基因上调，18个涉及离子转运蛋白或氨基酸转运蛋白的基因。我们重点关注并分析了一些与 p75NTR 信号传导相关的基因。2 抑制 p75NTR 诱导的负信号的肽的评估。a) 预期抑制之间结合的肽。研究了 RhoGDI 和 p75 以及 b) 预期抑制分拣蛋白和前脑源性神经营养因子 (BDNF) 之间结合的肽对脊髓损伤后运动活性的影响，但这两种肽均未能改善运动活性。脊髓损伤部位诱导的各种蛋白酶可能是肽降解的原因。3 p75NTR 基因修饰改善脊髓损伤……更多d 动物比较 p75NTR 基因破坏的小鼠（KO 小鼠）和野生小鼠之间脊髓损伤后运动能力的改善，KO 小鼠在前 8 天的运动能力得分高于野生小鼠，但此后差异消失。，表明 p75NTR 信号干扰了损伤早期的恢复。 4 条件性 p75NTR 转基因（Tg）小鼠的开发载体 DNA 在 loxp 基因之间含有终止密码子构建下游的p75NTR基因，并转移到受精卵中，因为导入的p75NTR基因只要不删除loxp之间的终止密码子就不会表达，因此动物很容易维持表达cre的转基因小鼠。酶基因以区域特异性方式与该p75NTR Tg小鼠杂交，p75NTR基因将在cre酶表达区域同时表达，该Tg动物将成为研究的有用工具。 p75NTR功能以后会少一些。