The effect of inflammatory stimuli on NMDA-related activation of glutamine synthase in human cultured astroglial cells

Carolina Muscoli, Valeria Visalli, Carmen Colica, Robert Nisticò, Ernesto Palma, Nicola Costa, Domenicantonio Rotiroti, Giuseppe Nisticò, Vincenzo Mollace

Research output: Contribution to journalArticle

Abstract

Removal of glutamate from the synaptic cleft by astroglial glutamine synthase (GS) is a crucial step in the regulation of glutamate turnover and metabolism, thus participating in endogenous neuroprotective processes occurring within brain tissues. Here we investigated on the effect of inflammatory cytokines on GS activity in astroglial cells undergoing NMDA receptors stimulation. Incubation of human cultured astroglial cells with NMDA (100 μM) enhanced GS expression, an effect driven by the generation of nitric oxide (NO) since L-NAME (500 μM), an inhibitor of NO synthase, reversed this effect. NMDA-related increase of GS activity and glutamine concentration was antagonised by previous incubation of astroglial cells with a mixture of LPS plus γIFN, an effect counteracted by dexamethasone, the latter effect being accompanied by inhibition of inducible NO synthase. These results show that LPS plus γIFN inhibit elevation of GS activity subsequent to NMDA receptor stimulation in astroglial cells via enhancement of inducible NO synthase, and this may represent the site of interaction between pro-inflammatory and excitotoxic stimuli in the brain.

Original languageEnglish
Pages (from-to)184-188
Number of pages5
JournalNeuroscience Letters
Volume373
Issue number3
DOIs
Publication statusPublished - Jan 20 2005

Keywords

  • Cytokine
  • Inflammation
  • Lipopolysaccaride
  • Nitric oxide
  • NMDA

ASJC Scopus subject areas

  • Neuroscience(all)

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