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, K. Abe

Research output: Contribution to journalReview articlepeer-review

56 Citations (Scopus)

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

Keywords

  • Adenovirus
  • Amyotrophic lateral sclerosis
  • GDNF
  • Gene therapy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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