Activation of multiple metabotropic glutamate receptor subtypes prevents NMDA-induced excitotoxicity in rat hippocampal slices

Marina Pizzi, Ornella Consolandi, Maurizio Memo, PierFranco Spano

Research output: Contribution to journalArticlepeer-review

Abstract

Metabotropic glutamate receptors (mGluRs) belong to a relative large receptor family consisting of multiple members with important roles in a number of brain functions. We report here that activation of mGluRs prevents the neurotoxic effect induced by N-methyl-D-aspartate (NMDA) in slices from the rat hippocampus. Neuroprotection was elicited when slices were simultaneously exposed to both the selective mGluR agonist (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD) and NMDA. Persisting stimulation of mGluRs after the toxic exposure did not improve the survival of pyramidal or granular cells. The neuroprotection elicited by tACPD was also evoked by its active isomer, (1S,3R)-ACPD, and was prevented by the selective mGluR antagonist (+)-α-methyl-4-carboxyphenyl-glycine (500 μM), confirming that mGluR activation is involved in the mechanism of action of tACPD. The effect of 100 μM tACPD was reproduced by 100 μM quisqualate, an agonist for mGluR1 and mGluR5, and by 1 μM of (2S,1's,2's)-2-carboxycyclopropyl-glycine, a preferential agonist of mGluR2 and mGluR3 subtypes. No neuroprotection was induced by L-2-amino-4-phosphonobutyrate, a selective agonist for mGluR4, mGluR6, mGluR7 and mGluR8, at 500 μM. Since the NMDA-mediated cell death in hippocampal slices is considered relevant to ischaemia-induced brain injury, these results indicate that mGluRs may be important safety devices used by neurons to decrease their sensitivity to excitotoxic stimuli and increase their chance of survival.

Original languageEnglish
Pages (from-to)1516-1521
Number of pages6
JournalEuropean Journal of Neuroscience
Volume8
Issue number7
DOIs
Publication statusPublished - 1996

Keywords

  • Hippocampus
  • L-AP4
  • L-CCG-I
  • MCPG
  • N-methyi-d-aspartate
  • Neurotoxicity
  • Quisqualate
  • tACPD

ASJC Scopus subject areas

  • Neuroscience(all)

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