Titre
Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Azzouz, M.
Auteure/Auteur
Hottinger, A.
Auteure/Auteur
Paterna, J. C.
Auteure/Auteur
Zurn, A. D.
Auteure/Auteur
Aebischer, P.
Auteure/Auteur
Bueler, H.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0964-6906
Statut éditorial
Publié
Date de publication
2000-03
Volume
9
Numéro
5
Première page
803
Dernière page/numéro d’article
11
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar 22
Research Support, Non-U.S. Gov't --- Old month value: Mar 22
Résumé
Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) underlie some familial cases of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by loss of cortical, brainstem and spinal motoneurons. Transgenic mice over- expressing a mutated form of human SOD1 containing a Gly-->Ala substitution at position 93 (SOD1(G93A)) develop a severe, progressive motoneuron disease. We investigated the potential of recombinant adeno-associated virus (rAAV) to transfer neuroprotective molecules in this animal ALS model. Initial experiments showed that injection of an rAAV vector encoding green fluorescent protein unilaterally into the lumbar spinal cord of wild-type mice leads to expression of the reporter gene in 34.7 +/- 5.2% of the motoneurons surrounding the injection site. Intraspinal injection of an rAAV encoding the anti-apoptotic protein bcl-2 in SOD1 (G93A) mice resulted in sustained bcl-2 expression in motoneurons and significantly increased the number of surviving motoneurons at the end-stage of disease. Moreover, the compound muscle action potential amplitude elicited by nerve stimulation and recorded by electromyographic measurements was higher in the rAAV-bcl-2-treated group than in controls. Local bcl-2 expression in spinal motoneurons delayed the appearance of signs of motor deficiency but was not sufficient to prolong the survival of SOD1 (G93A) mice. To our know-ledge, this study describes the first successful transduction and protection of spinal motoneurons by direct gene transfer in a model of progressive motoneuron disease. Our results support the use of AAVs for the delivery of protective genes to spinal cord moto-neurons as a possible way to enhance motoneuron survival and repair.
Sujets
PID Serval
serval:BIB_F4FBC793D3AB
PMID
Open Access
Oui
Date de création
2008-01-28T07:44:13.814Z
Date de création dans IRIS
2025-05-21T06:53:34Z
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Nom
REF.pdf
Version du manuscrit
published
Taille
805.03 KB
Format
Adobe PDF
PID Serval
serval:BIB_F4FBC793D3AB.P001
URN
urn:nbn:ch:serval-BIB_F4FBC793D3AB2
Somme de contrôle
(MD5):d02dfc5e12c653d3759a435dab835b1d