Glial cell line-derived neurotrophic factor protein prevents motor neuron loss of transgenic model mice for amyotrophic lateral sclerosis

Yasuhiro Manabe, I. Nagano, A. Gazi, T. Murakami, M. Shiote, M. Shoji, H. Kitagawa, K. Abe

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Effects of glial cell line-derived neurotrophic factor (GDNF) were studied in transgenic (Tg) mice model for amyotrophic lateral sclerosis. GDNF protein or vehicle was injected three times a week from 35 weeks of age into the right gastrocnemius muscle of Tg mice carrying mutant human Cu/Zn superoxide dismutase gene, and histological analysis was performed at 46 weeks. Clinical data showed a tendency of improvement, but was not significantly different between the two animal groups. In contrast, total number of and phospho-Akt (p-Akt) positive large motor neurons in the treated side was significantly more preserved in GDNF-treated group than in vehicle group (p < 0.05). Immunoreactivity of phospho-ERK and active caspases-3 and -9 showed no difference. These results indicate that the intramuscular injection of GDNF protein prevented motor neuron loss while 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)195-200
Number of pages6
JournalNeurological Research
Volume25
Issue number2
DOIs
Publication statusPublished - Mar 2003

Keywords

  • Amyotrophic lateral sclerosis
  • GDNF
  • Therapy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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