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

Details

Serval ID
serval:BIB_F7B822E6181B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo.
Journal
Journal of Neuroscience
Author(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
Publication state
Published
Issued date
2006
Volume
26
Number
22
Pages
5978-5989
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
24/01/2008 14:26
Last modification date
20/08/2019 16:23
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