Prevention of motoneuron death by adenovirus-mediated neurotrophic factors
Autor: | Jacques Mallet, Alain Privat, Minerva Giménez y Ribotta, Frédéric Revah, Isabelle Loquet, Laurent Pradier |
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Rok vydání: | 1997 |
Předmět: |
Genetic Vectors
Nerve Tissue Proteins Ciliary neurotrophic factor Adenoviridae Rats Sprague-Dawley Cellular and Molecular Neuroscience Neurotrophic factors Glial cell line-derived neurotrophic factor Animals Medicine Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Amyotrophic lateral sclerosis Motor Neurons Cell Death biology business.industry Brain-Derived Neurotrophic Factor Gene Transfer Techniques beta-Galactosidase medicine.disease Denervation Axons Rats Facial Nerve Neuroprotective Agents Animals Newborn biology.protein business Neuroscience |
Zdroj: | Journal of Neuroscience Research. 48:281-285 |
ISSN: | 1097-4547 0360-4012 |
DOI: | 10.1002/(sici)1097-4547(19970501)48:3<281::aid-jnr11>3.0.co;2-4 |
Popis: | 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%, P0.05) ou GDNF (41.9%, P0.05) 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. |
Databáze: | OpenAIRE |
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