Modulation of astrocytic metabolic phenotype by proinflammatory cytokines

Mathilde Gavillet, Igor Allaman*, Pierre J. Magistretti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Astrocytes play an important role in nervous system homeostasis. In particular, they contribute to the regulation of local energy metabolism and to oxidative stress defence. In previous experiments, we showed that long-term treatment with interleukin lot (IL-1α) or tumor necrosis factor-α (TNFα) alone increases glucose utilization in primary culture of mouse astrocytes. In our study, we report that a combination of IL-1β and TNFα exerts a synergistic effect on glucose utilization and markedly modifies the metabolic phenotype of astrocytes. Thus, IL-1β+TNFα treated astrocytes show a marked decrease in glycogen levels, a slight but not significant decrease in lactate release as well as a massive increase in both the pentose phosphate pathway and TCA cycle activities. Glutamate-stimulated glucose utilization and lactate release, a typical feature of astrocyte energy metabolism, are altered after pretreatment with IL-1β+TNFα As far as mechanisms for oxidative stress defence are concerned, we observed that treatment with IL-1β+TNFα decreases cellular glutathione content and increases glutathione release into the extracellular space while stimulating superoxide anion and nitric oxide production as well as H2O2 release. Interestingly, stimulation of glucose utilization by IL-1β+TNFα is not affected by the antioxidant N-acetyl-L-cysteine, suggesting that cellular stress does not account for this effect. Finally, the effects of cytokines on glucose utilization appear to involve multiple signaling cascades including the phosphoinositide 3-kinase and mitogen-activated protein kinases. Taken together these results establish that a proinflammatory environment such as observed in several neuropathological conditions including Alzheimer's disease, markedly modifies the metabolic phenotype of astrocytes.

Original languageEnglish (US)
Pages (from-to)975-989
Number of pages15
JournalGLIA
Volume56
Issue number9
DOIs
StatePublished - Jul 2008
Externally publishedYes

Keywords

  • Energy metabolism
  • Glia
  • Neurodegeneration
  • Neuroinflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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