Adenoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus.
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 beta-galactosidase gene) or PBS was inoculated into the jugular foramen. Four days after the avulsion and treatment with AxCALacZ, the animals expressed beta-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.
Saito
Koichiro
K
Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 1608582, Japan.
Shiotani
Akihiro
A
Watabe
Kazuhiko
K
Moro
Kazuhisa
K
Fukuda
Hiroyuki
H
Ogawa
Kaoru
K
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D007839:Functional Laterality; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D023421:Models, Animal; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects; D009414:Nerve Growth Factors / Q000235:genetics* / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology; D061223:Vagus Nerve Injuries
C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018697:Nootropic Agents; D011994:Recombinant Proteins; D008058:Dihydrolipoamide Dehydrogenase; D002795:Choline O-Acetyltransferase