Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents motor neuron loss of transgenic model mice for amyotrophic lateral sclerosis

Y. Manabe, I. Nagano, M. S A Gazi, T. Murakami, M. Shiote, M. Shoji, H. Kitagawa, Y. Setoguchi, Koji Abe

Research output: Contribution to journalArticle

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Abstract

Effects of adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF) were studied in transgenic (Tg) mice model for amyotrophic lateral sclerosis (ALS). Adenoviral vector containing GDNF gene (Ad-GDNF), E. coli lacZ (Ad-LacZ), or vehicle was injected once a week from 35 weeks of age into the right gastrocnemius muscle of Tg mice carrying mutant human Cu/Zn superoxide dismutase (SOD1) gene, and histological analysis was performed at 46 W. Clinical data showed a tendency of improvement, but was not significantly different among the three animal groups. In contrast, total number of and phospho-Akt (p-Akt) positive large motor neurons in the treated side was significantly preserved in Ad-GDNF-treated group than in vehicle- and Ad-LacZ-treated groups (*p <0.05). Immunoreactivity of phospho-ERK (p-ERK) and active caspases-3 and -9 showed no difference. These results indicate that the Ad-GDNF treatment prevented motor neuron loss with preserving survival p-Akt signal and without affecting caspase activations, suggesting a future possibility for the therapy of the disease.

Original languageEnglish
Pages (from-to)329-334
Number of pages6
JournalApoptosis
Volume7
Issue number4
DOIs
Publication statusPublished - 2002

Fingerprint

Gene transfer
Glial Cell Line-Derived Neurotrophic Factor
Amyotrophic Lateral Sclerosis
Motor Neurons
Adenoviridae
Transgenic Mice
Neurons
Genes
Escherichia coli
Caspase 9
Caspases
Caspase 3
Muscle
Animals
Skeletal Muscle
Chemical activation
Survival

Keywords

  • Adenovirus
  • Amyotrophic lateral sclerosis
  • GDNF
  • Gene therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents motor neuron loss of transgenic model mice for amyotrophic lateral sclerosis. / Manabe, Y.; Nagano, I.; Gazi, M. S A; Murakami, T.; Shiote, M.; Shoji, M.; Kitagawa, H.; Setoguchi, Y.; Abe, Koji.

In: Apoptosis, Vol. 7, No. 4, 2002, p. 329-334.

Research output: Contribution to journalArticle

Manabe, Y. ; Nagano, I. ; Gazi, M. S A ; Murakami, T. ; Shiote, M. ; Shoji, M. ; Kitagawa, H. ; Setoguchi, Y. ; Abe, Koji. / Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents motor neuron loss of transgenic model mice for amyotrophic lateral sclerosis. In: Apoptosis. 2002 ; Vol. 7, No. 4. pp. 329-334.
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