Glucocorticoids modulate neurotransmitter-induced glycogen metabolism in cultured cortical astrocytes

Igor Allaman*, Luc Pellerin, Pierre Magistretti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Glucocorticoids (GC) are considered as key modulators of glycogen homeostasis in peripheral tissues, but their role in the central nervous system has only partially been characterized. Exposure of primary cultures of cortical astrocytes to dexamethasone (DEX), a synthetic glucocorticoid, results in the reduction of noradrenaline (NA)-induced glycogen synthesis in a concentration-dependent manner with a IC50 of 4.88 nM and a maximum inhibition of 51%. Such an effect is mediated via glucocorticoid receptors (GRs), since it is mimicked by the glucocorticoid analogue RU28362 (100 nM) and prevented by the GR antagonist RU38486 (1 μM). DEX does not act through alteration of signal transduction mechanisms, as cAMP formation induced by noradrenergic stimulation was unchanged. Moreover, glycogen synthesis was inhibited to the same extent when DEX was applied either together or only after a brief NA application. Neither [3H]2-deoxyglucose uptake nor lactate release was altered by DEX in the presence of NA, demonstrating that inhibition of glycogen synthesis is not a consequence of reduced glucose utilization or availability. Interestingly, enhancement of glycogen synthase activity induced by NA was reduced in the presence of DEX (-27%). These results suggest that GC could have a significant influence on neuroenergetics as they could modulate activity-related changes in brain glycogen metabolism.

Original languageEnglish (US)
Pages (from-to)900-908
Number of pages9
JournalJournal of Neurochemistry
Volume88
Issue number4
StatePublished - Feb 1 2004

Keywords

  • Dexamethasone
  • Energy metabolism
  • Glia
  • Glycogen synthase
  • Noradrenaline
  • Protein targeting to glycogen

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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