Adenoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus

Koichiro Saito, Akihiro Shiotani, Kazuhiko Watabe, Kazuhisa Moro, Hiroyuki Fukuda, Kaoru Ogawa

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

We examined neuroprotective effects of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat motoneurons in the nucleus ambiguus. After vagal nerve avulsion, AxCAhGDNF, AxCALacZ (adenovirus encoding β-galactosidase gene) or PBS was inoculated into the jugular foramen. Four days after the avulsion and treatment with AxCALacZ, the animals expressed β-galactosidase activity in the lesioned motoneurons in the nucleus ambiguus. The animals avulsed and inoculated with AxCAhGDNF showed immunolabeling for GDNF in the nucleus ambiguus on the treated side and expression of virus-induced human GDNF mRNA transcripts in the brainstem tissue that contained the nucleus ambiguus of the treated side. The treatment with AxCAhGDNF after avulsion prevented the loss of lesioned motoneurons in the nucleus ambiguus, ameliorated the choline acetyltransferase immunoreactivity, and also suppressed the activity of nitric oxide synthase in these neurons. These results indicate that adenovirus-mediated GDNF gene transfer may prevent the degeneration of motoneurons in humans after either vagal nerve injury or recurrent laryngeal nerve injury.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalBrain Research
Volume962
Issue number1-2
DOIs
Publication statusPublished - 2003 Feb 7

Keywords

  • Adenovirus
  • Avulsion
  • GDNF
  • Laryngeal paralysis
  • Motoneuron
  • Nucleus ambiguus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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