Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic mice
✍ Scribed by Hisashi Narai; Isao Nagano; Hristeina Ilieva; Mito Shiote; Tetsuya Nagata; Takeshi Hayashi; Mikio Shoji; Koji Abe
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 921 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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-1Rb 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-1Rb 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 IGF-1R and the main downstream signal, IRS-1.