Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents motor neuron loss of transgenic model mice for amyotrophic lateral sclerosis |
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Authors: | Manabe Yasuhiro Nagano I Gazi M S A Murakami T Shiote M Shoji M Kitagawa H Setoguchi Y Abe K |
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Affiliation: | (1) Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan;(2) Tokushima New Drug Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan;(3) Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan |
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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. |
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Keywords: | adenovirus amyotrophic lateral sclerosis GDNF gene therapy |
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