title: Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents motor neuron loss of transgenic model mice for amyotrophic lateral sclerosis.
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.
authors.affiliation: Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. manabe@cc.okayama-u.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Manabe
authors.forename: I
authors.initials: I
authors.lastname: Nagano
authors.forename: M S A
authors.initials: MS
authors.lastname: Gazi
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Shiote
authors.forename: M
authors.initials: M
authors.lastname: Shoji
authors.forename: H
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Setoguchi
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D000256:Adenoviridae; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D016923:Cell Death / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000627:therapeutic use; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology
chemical_list: C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors