Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability.

Détails

Ressource 1Télécharger: 3326.full.pdf (1997.09 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_D1311F834070
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability.
Périodique
The Journal of neuroscience
Auteur(s)
Allaman I., Gavillet M., Bélanger M., Laroche T., Viertl D., Lashuel H.A., Magistretti P.J.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
03/03/2010
Peer-reviewed
Oui
Volume
30
Numéro
9
Pages
3326-3338
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Amyloid-beta (Abeta) peptides play a key role in the pathogenesis of Alzheimer's disease and exert various toxic effects on neurons; however, relatively little is known about their influence on glial cells. Astrocytes play a pivotal role in brain homeostasis, contributing to the regulation of local energy metabolism and oxidative stress defense, two aspects of importance for neuronal viability and function. In the present study, we explored the effects of Abeta peptides on glucose metabolism in cultured astrocytes. Following Abeta(25-35) exposure, we observed an increase in glucose uptake and its various metabolic fates, i.e., glycolysis (coupled to lactate release), tricarboxylic acid cycle, pentose phosphate pathway, and incorporation into glycogen. Abeta increased hydrogen peroxide production as well as glutathione release into the extracellular space without affecting intracellular glutathione content. A causal link between the effects of Abeta on glucose metabolism and its aggregation and internalization into astrocytes through binding to members of the class A scavenger receptor family could be demonstrated. Using astrocyte-neuron cocultures, we observed that the overall modifications of astrocyte metabolism induced by Abeta impair neuronal viability. The effects of the Abeta(25-35) fragment were reproduced by Abeta(1-42) but not by Abeta(1-40). Finally, the phosphoinositide 3-kinase (PI3-kinase) pathway appears to be crucial in these events since both the changes in glucose utilization and the decrease in neuronal viability are prevented by LY294002, a PI3-kinase inhibitor. This set of observations indicates that Abeta aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability.
Mots-clé
Alzheimer Disease/metabolism, Alzheimer Disease/pathology, Alzheimer Disease/physiopathology, Amyloid beta-Peptides/metabolism, Amyloid beta-Peptides/toxicity, Animals, Animals, Newborn, Astrocytes/drug effects, Astrocytes/metabolism, Brain/metabolism, Brain/pathology, Brain/physiopathology, Cell Communication/drug effects, Cell Communication/physiology, Cell Survival/drug effects, Cell Survival/physiology, Cells, Cultured, Energy Metabolism/drug effects, Energy Metabolism/physiology, Free Radicals/metabolism, Glucose/metabolism, Glutathione/metabolism, Hydrogen Peroxide/metabolism, Mice, Nerve Degeneration/metabolism, Nerve Degeneration/pathology, Nerve Degeneration/physiopathology, Neurons/metabolism, Oxidative Stress/drug effects, Oxidative Stress/physiology, Peptide Fragments/toxicity, Phenotype, Phosphatidylinositol 3-Kinases/antagonists & inhibitors, Phosphatidylinositol 3-Kinases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/04/2010 11:56
Dernière modification de la notice
20/08/2019 16:51
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