Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo.

Détails

ID Serval
serval:BIB_F7B822E6181B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo.
Périodique
Journal of Neuroscience
Auteur(s)
Escartin C., Brouillet E., Gubellini P., Trioulier Y., Jacquard C., Smadja C., Knott G.W., Kerkerian-Le Goff L., Déglon N., Hantraye P., Bonvento G.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
2006
Volume
26
Numéro
22
Pages
5978-5989
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
To study the functional role of activated astrocytes in glutamate homeostasis in vivo, we used a model of sustained astrocytic activation in the rat striatum through lentiviral-mediated gene delivery of ciliary neurotrophic factor (CNTF). CNTF-activated astrocytes were hypertrophic, expressed immature intermediate filament proteins and highly glycosylated forms of their glutamate transporters GLAST and GLT-1. CNTF overexpression produced a redistribution of GLAST and GLT-1 into raft functional membrane microdomains, which are important for glutamate uptake. In contrast, CNTF had no detectable effect on the expression of a number of neuronal proteins and on the spontaneous glutamatergic transmission recorded from striatal medium spiny neurons. These results were replicated in vitro by application of recombinant CNTF on a mixed neuron/astrocyte striatal culture. Using microdialysis in the rat striatum, we found that the accumulation of extracellular glutamate induced by quinolinate (QA) was reduced threefold with CNTF. In line with this result, CNTF significantly increased QA-induced [(18)F]-fluoro-2-deoxyglucose uptake, an indirect index of glutamate uptake by astrocytes. Together, these data demonstrate that CNTF activation of astrocytes in vivo is associated with marked phenotypic and molecular changes leading to a better handling of increased levels of extracellular glutamate. Activated astrocytes may therefore be important prosurvival agents in pathological conditions involving defects in glutamate homeostasis.
Mots-clé
Animals, Astrocytes/cytology, Astrocytes/drug effects, Ciliary Neurotrophic Factor/genetics, Ciliary Neurotrophic Factor/pharmacology, Coculture Techniques, Corpus Striatum/drug effects, Corpus Striatum/physiology, Excitatory Amino Acid Transporter 1/drug effects, Excitatory Amino Acid Transporter 1/physiology, Excitatory Amino Acid Transporter 2/drug effects, Excitatory Amino Acid Transporter 2/physiology, Genetic Vectors, Glutamic Acid/physiology, Humans, Lentivirus/genetics, Male, Membrane Microdomains/drug effects, Membrane Microdomains/physiology, Neurons/cytology, Neurons/drug effects, Rats, Rats, Inbred Lew
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:26
Dernière modification de la notice
09/05/2019 3:39
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