Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic mice

Hisashi Narai, Isao Nagano, Hristeina Ilieva, Mito Shiote, Tetsuya Nagata, Takeshi Hayashi, Mikio Shoji, Koji Abe

Research output: Contribution to journalArticle

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Abstract

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-1Rβ and the key intracellular downstream protein insulin receptor substrate-1 (IRS-1) by using SOD1G93A 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-1Rβ 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.

Original languageEnglish
Pages (from-to)452-457
Number of pages6
JournalJournal of Neuroscience Research
Volume82
Issue number4
DOIs
Publication statusPublished - Nov 15 2005

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Motor Neurons
Somatomedins
Transgenic Mice
Signal Transduction
Insulin Receptor Substrate Proteins

Keywords

  • Amyotrophic lateral sclerosis
  • Immunohistochemistry
  • Insulin receptor substrate-1
  • Insulin-like growth factor-1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic mice. / Narai, Hisashi; Nagano, Isao; Ilieva, Hristeina; Shiote, Mito; Nagata, Tetsuya; Hayashi, Takeshi; Shoji, Mikio; Abe, Koji.

In: Journal of Neuroscience Research, Vol. 82, No. 4, 15.11.2005, p. 452-457.

Research output: Contribution to journalArticle

Narai, Hisashi ; Nagano, Isao ; Ilieva, Hristeina ; Shiote, Mito ; Nagata, Tetsuya ; Hayashi, Takeshi ; Shoji, Mikio ; Abe, Koji. / Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic mice. In: Journal of Neuroscience Research. 2005 ; Vol. 82, No. 4. pp. 452-457.
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