Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic mice
Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic mice
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DOI：
10.1002/jnr.20668
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发表时间：
2005-11-15
影响因子：
4.2
通讯作者：
Abe, K
中科院分区：
文献类型：
--
作者：
Narai, H;Nagano, I;Abe, K
胰岛素样生长因子-1（IGF-1）在肌萎缩侧索硬化症（ALS）中的作用及其作用机制从致病和治疗的角度来看都很重要。本研究采用SOD 1（G93 A）转基因小鼠鞘内连续注射IGF-1，观察IGF-1 RP和细胞内关键下游蛋白胰岛素受体底物-1（IRS-1）的变化。IGF-1处理以剂量依赖性方式保留了腰椎运动神经元的数量。IGF-1 R β和IRS-1免疫阳性运动神经元的数量在野生型和Tg小鼠与溶剂处理之间没有显著差异，而用IGF-1处理Tg小鼠以剂量依赖性方式减少免疫阳性运动神经元的数量。另一方面，与野生型小鼠相比，溶媒处理的Tg小鼠中溶媒处理小鼠中免疫阳性运动神经元/总活运动神经元的比率大大增加。在IGF-1处理的情况下，该比率以剂量依赖性方式显著降低。这些结果表明，IGF-1治疗通过影响经由IGF-1 R和主要下游信号IRS-1的信号转导系统来防止运动神经元损失。(c)2005 Wiley-Liss，Inc.
The role of insulin-like growth factor-1 (IGF-1) in amyotrophic lateral sclerosis (ALS) and its mechanism of action are important from both pathogenic and therapeutic points of view. The present study investigated the changes of IGF-1 RP and the key intracellular downstream protein insulin receptor substrate-1 (IRS-1) by using SOD1(G93A) transgenic mice with continuous intrathecal IGF-1 treatment. The number of lumbar spinal motor neurons was preserved with IGF-1 treatment in a dose-dependent manner. The numbers of immunopositive motor neurons for IGF-1R beta and IRS-1 were not significantly different between wild-type and Tg mice with vehicle treatment, whereas treatment of Tg mice with IGF-1 decreased the numbers of immunopositive motor neurons in a dose-dependent manner. On the other hand, the ratio of immunopositive motor neurons per total living motor neurons in vehicle-treated mice was greatly increased in Tg mice with vehicle treatment compared with wild-type mice. With IGF-1 treatment, the ratio was dramatically decreased in a dose-dependent manner. These results suggest that IGF-1 treatment prevents motor neuron loss by affecting the signal transduction system through lGF-1R and the main downstream signal, IRS-1. (c) 2005 Wiley-Liss, Inc.