Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus.

Détails

Ressource 1Télécharger: 5587.full.pdf (654.88 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_EEF5328332E6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus.
Périodique
Journal of Neuroscience
Auteur(s)
Hottinger A.F., Azzouz M., Déglon N., Aebischer P., Zurn A.D.
ISSN
0270-6474 (Print)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
08/2000
Volume
20
Numéro
15
Pages
5587-5593
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
To date, delivery of neurotrophic factors has only allowed to transiently protect axotomized facial motoneurons against cell death. In the present report, long-term protection of these neurons was evaluated by continuously expressing the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) within the facial nucleus using a lentiviral vector system. The viral vector was injected unilaterally into the facial nucleus of 4-month-old Balb/C mice. In contrast to axotomy in other adult rodents, facial nerve lesion in these animals leads to a progressive and sustained loss and/or atrophy of >50% of the motoneurons. This model thus represents an attractive model to evaluate potential protective effects of neurotrophic factors for adult-onset motoneuron diseases, such as amyotrophic lateral sclerosis. One month after unilateral lentiviral vector injection, the facial nerve was sectioned, and the animals were killed 3 months later. Viral delivery of the GDNF gene led to long-term expression and extensive diffusion of GDNF within the brainstem. In addition, axotomized motoneurons were completely protected against cell death, because 95% of the motoneurons were present as demonstrated by both Nissl staining and choline acetyltransferase immunoreactivity. Furthermore, GDNF prevented lesion-induced neuronal atrophy and maintained proximal motoneuron axons, despite the absence of target cell reinnervation. This is the first evidence that viral-mediated delivery of GDNF close to the motoneuron cell bodies of the facial nucleus of adult mice can lead to complete and long-term protection against lesion-induced cell death.
Mots-clé
Age Factors, Animals, Axotomy, Cell Survival/genetics, Choline O-Acetyltransferase/analysis, Facial Nerve/cytology, Facial Nerve/physiology, Facial Nerve Injuries/physiopathology, Gene Expression Regulation, Viral, Genetic Therapy, Genetic Vectors, Glial Cell Line-Derived Neurotrophic Factor, Lac Operon, Lentivirus/genetics, Mice, Mice, Inbred BALB C, Motor Neurons/chemistry, Motor Neurons/cytology, Nerve Growth Factors, Nerve Tissue Proteins/genetics, Neurofilament Proteins/analysis, Neuroprotective Agents/metabolism, Transgenes/physiology, beta-Galactosidase/genetics
Pubmed
Web of science
Création de la notice
28/01/2008 9:44
Dernière modification de la notice
03/03/2018 22:33
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