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Keywords:

  • astrocyte;
  • calcium;
  • GDNF;
  • ifenprodil;
  • IL-1β;
  • NMDA

J. Neurochem. (2011) 119, 686–696.

Abstract

Glial cell line-derived neurotrophic factor (GDNF) plays an important role in neuroinflammatory and neuropathic pain conditions. Astrocytes produce and secrete GDNF, which interacts with its receptors to induce Ca2+ transients. This study aimed first to assess intracellular Ca2+ responses of astrocytes in primary culture when exposed to the neuroprotective and anti-inflammatory peptide GDNF. Furthermore, incubation with the inflammatory inducers lipopolysaccharide (LPS), NMDA, or interleukin 1-β (IL-1β) attenuated the GDNF-induced Ca2+ transients. The next aim was to try to restore the suppressed GDNF responses induced by inflammatory changes in the astrocytes with an anti-inflammatory substance. Ifenprodil, an NMDA receptor antagonist at the NR2B subunit, was tested. It was shown to restore the GDNF-evoked Ca2+ transients and increased the Na+/K+-ATPase expression. Ifenprodil seems to be a potent anti-inflammatory substance for astrocytes which have been pre-activated by inflammatory stimuli.