Adenoviral vector-mediated GDNF gene transfer prevents death of adult facial motoneurons.
We examined neuroprotective effects of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat facial motoneurons. After facial nerve avulsion, animals locally injected into the facial canal with AxCALacZ (adenovirus encoding beta-galactosidase gene) or AxCAhGDNF showed expression of beta-galactosidase activity or intense immunolabeling for GDNF in lesioned facial motoneurons, respectively. The treatment with AxCAhGDNF after avulsion significantly prevented the loss of lesioned facial motoneurons, ameliorated choline acetyltransferase immunoreactivity, and suppressed the activity of nitric oxide synthase in these neurons. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with peripheral nerve injury and motor neuron diseases.
Sakamoto
T
T
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan.
Watabe
K
K
Ohashi
T
T
Kawazoe
Y
Y
Oyanagi
K
K
Inoue
K
K
Eto
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005154:Facial Nerve / Q000473:pathology / Q000503:physiopathology*; D020220:Facial Nerve Injuries / Q000473:pathology / Q000503:physiopathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D009046:Motor Neurons / Q000201:enzymology / Q000502:physiology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D011916:Rats, Inbred F344
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D002795:Choline O-Acetyltransferase