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Caractérisation phénotypique et fonctionnelle de l'activation astrocytaire induite par transfert lentiviral du CNTF in vivo: Implications pour la survie neuronale

Carole Escartin 1
1 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
MIRCEN - Service MIRCEN : DRF/JACOB, CNRS - Centre National de la Recherche Scientifique : UMR 9199
Abstract : Astrocytes play an active role in brain function. They provide metabolic and trophic support to neurons and control the entry of metabolites inside brain parenchyma. Through their glutamate transporters GLAST and GLT-1, astrocytes are also responsible of the uptake and recycling of glutamate, the main excitatory neurotransmitter but also a potential neurotoxic agent. Astrocytes become activated in response to various pathological situations. This brain hallmark has been known for a long time, however, its functional consequences are still a matter of debate. Does activation of astrocytes represent a protective and adaptive mechanism to face deleterious conditions or does it play a role in neuronal degeneration? We have developed an in vivo model of astrocytic activation in the rat striatum through lentiviral gene tranfer of Ciliary Neurotrophic Factor (CNTF), an endogenous activator of astrocytes. Using this stable and reproducible model of astrocytes activation, we observed marked alterations in brain energy metabolism, with a shift from glycolysis to the ketone bodies pathway. In addition, CNTF activation of astrocytes induced several changes in glutamate uptake machinery. Astroglial transporters were highly glycosylated and redistributed into raft microdomains. During an excitotoxic process, glutamate handling, energetic supply and neuronal survival were significantly improved. These results underline the beneficial role of activated astrocytes that have a prosurvival phenotype and function towards neurons. This study gives new clues (1) to delineate the role and the interest of activated astrocytes in pathological processes and (2) to characterize the effects of CNTF, which is a therapeutic candidate for several neurodegenerative diseases.
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https://tel.archives-ouvertes.fr/tel-00433114
Contributor : Carole Escartin <>
Submitted on : Wednesday, November 18, 2009 - 11:15:48 AM
Last modification on : Monday, December 14, 2020 - 9:52:37 AM
Long-term archiving on: : Thursday, June 17, 2010 - 8:48:58 PM

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  • HAL Id : tel-00433114, version 1

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Carole Escartin. Caractérisation phénotypique et fonctionnelle de l'activation astrocytaire induite par transfert lentiviral du CNTF in vivo: Implications pour la survie neuronale. Neurosciences [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2006. Français. ⟨tel-00433114⟩

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