Prevention of motoneuron death by adenovirus-mediated neurotrophic factors.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motoneurons, and has no effective treatment. Experimental studies in rodents have shown that motoneurons respond to a variety of molecules including brain-derived neurotrophic factor (BDNF). and the glial-cell line-derived neurotrophic factor (GDNF). Here we investigated the neuroprotective effect of these growth factors, encoded by an adenovirus, on the death of axotomized facial motoneurons in newborn rats. We used a new gene therapy strategy that involves gene transfer to motoneurons by intramuscular injection of an adenoviral vector, which is retrogradely transported from injected target muscle (Finiels et al.,: NeuroReport 7:373-378, 1995). A significant increased survival of motoneurons was observed in animals pretreated with adenovirus encoding BDNF (34.5%, P < 0.05) ou GDNF (41.9%, P < 0.05) 1 week after axotomy. These results indicate that pretreatment with BDNF or GDNF, using this therapeutic strategy, is able to prevent the massive death of motoneurons that normally follows axotomy in the neonatal period, opening new perspectives to limit neuronal death in degenerative disorders.
Giménez y Ribotta
M
M
INSERM U. 336, DPVSN, University of Montpellier, France.
Revah
F
F
Pradier
L
L
Loquet
I
I
Mallet
J
J
Privat
A
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D003714:Denervation; D005154:Facial Nerve / Q000166:cytology / Q000201:enzymology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D001616:beta-Galactosidase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D001616:beta-Galactosidase