The neuroprotective activity of group-II metabotropic glutamate receptors requires new protein synthesis and involves a glial-neuronal signaling

Valeria Bruno, Francesc X. Sureda, Marianna Storto, Giacomo Casabona, Alessandra Caruso, Thomas Knopfel, Rainer Kuhn, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

The group-II metabotropic glutamate (mGlu) receptor agonists (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), S-4-carboxy- 3-hydroxyphenylglycine (4C3H PG), and (2S, 1'S,2'S)-2- (carboxycyclopropyl)glycine (L-CCG-I) protected mouse cortical neurons grown in mixed cultures against excitotoxic degeneration induced by a 10 min pulse with NMDA. Protection was observed not only when agonists were added in combination with NMDA but also when they were transiently applied to cultures 6-20 hr before the NMDA pulse. In both cases, neuroprotection was reduced by the group-II mGlu receptor antagonist (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'- phenylcyclopropyl)glycine (PCCG-IV), as well as by the protein synthesis inhibitor cycloheximide (CHX). Both neurons and astrocytes in mixed cultures were immunostained with an antibody that recognized mGlu2 and mGlu3 receptors in recombinant cells. To determine whether astrocytes played any role in the neuroprotection mediated by group-II mGlu receptors, we exposed pure cultures of cortical astrocytes to DCG-IV, 4C3HPG, or L-CCG-I for 10 min. The astrocyte medium collected 2-20 hr after the exposure to any of these drugs was highly neuroprotective when transferred to mixed cultures treated with NMDA. This protective activity was reduced when CHX was applied to astrocyte cultures immediately after the transient exposure to group-II mGlu receptor agonists. We conclude that neuroprotection mediated by group-II mGlu receptors in cultured cortical cells requires new protein synthesis and involves an interaction between neurons and astrocytes.

Original languageEnglish
Pages (from-to)1891-1897
Number of pages7
JournalJournal of Neuroscience
Volume17
Issue number6
Publication statusPublished - Mar 15 1997

Keywords

  • astrocytes
  • cortical cultures
  • excitotoxicity
  • metabotropic glutamate receptors
  • neuroprotection
  • new protein synthesis

ASJC Scopus subject areas

  • Neuroscience(all)

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