QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (85) Citing Articles via Google Scholar Google Scholar Articles by Bruno, V. Articles by Nicoletti, F. Search for Related Content PubMed PubMed Citation Articles by Bruno, V. Articles by Nicoletti, F.

Next Article 

Volume 17, Number 6, Issue of March 15, 1997 pp. 1891-1897
Copyright ©1997 Society for Neuroscience

The Neuroprotective Activity of Group-II Metabotropic Glutamate Receptors Requires New Protein Synthesis and Involves a Glial-Neuronal Signaling

Received Aug. 13, 1996; revised Dec. 5, 1996; accepted Dec. 11, 1996.

Valeria Bruno¹, Francesc X. Sureda¹, Marianna Storto¹, Giacomo Casabona¹, Alessandra Caruso², Thomas Knopfel³, Rainer Kuhn⁴, and Ferdinando Nicoletti^{1, 3}

¹ I. N. M. Neuromed, Pozzilli, Italy, ² Institute of Biochemistry, School of Medicine, and ³ Institute of Pharmacology, School of Pharmacy, University of Catania, 95125 Catania Italy, and ⁴ CNS Department, Ciba Research Laboratories, Basel, Switzerland

The group-II metabotropic glutamate (mGlu) receptor agonists (2S,1R,2R,3R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), S-4-carboxy-3-hydroxyphenylglycine (4C3HPG), and (2S,1S,2S)-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,1S,2S,3R)-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.

Key words: cortical cultures; metabotropic glutamate receptors; excitotoxicity; astrocytes; neuroprotection; new protein synthesis

This article has been cited by other articles:

				C. Corti, G. Battaglia, G. Molinaro, B. Riozzi, A. Pittaluga, M. Corsi, M. Mugnaini, F. Nicoletti, and V. Bruno The Use of Knock-Out Mice Unravels Distinct Roles for mGlu2 and mGlu3 Metabotropic Glutamate Receptors in Mechanisms of Neurodegeneration/Neuroprotection J. Neurosci., August 1, 2007; 27(31): 8297 - 8308. [Abstract] [Full Text] [PDF]

				D. L. Taylor, L. T. Diemel, and J. M. Pocock Activation of Microglial Group III Metabotropic Glutamate Receptors Protects Neurons against Microglial Neurotoxicity J. Neurosci., March 15, 2003; 23(6): 2150 - 2160. [Abstract] [Full Text] [PDF]

				B. Dziedzic, V. Prevot, A. Lomniczi, H. Jung, A. Cornea, and S. R. Ojeda Neuron-to-Glia Signaling Mediated by Excitatory Amino Acid Receptors Regulates ErbB Receptor Function in Astroglial Cells of the Neuroendocrine Brain J. Neurosci., February 1, 2003; 23(3): 915 - 926. [Abstract] [Full Text] [PDF]

				A. Bond, N. M. Jones, C. A. Hicks, G. M. Whiffin, M. A. Ward, M. F. O'Neill, A. E. Kingston, J. A. Monn, P. L. Ornstein, D. D. Schoepp, et al. Neuroprotective Effects of LY379268, a Selective mGlu2/3 Receptor Agonist: Investigations into Possible Mechanism of Action In Vivo J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 800 - 809. [Abstract] [Full Text]

				V. Bruno, G. Battaglia, I. Ksiazek, H. van der Putten, M. V. Catania, R. Giuffrida, S. Lukic, T. Leonhardt, W. Inderbitzin, F. Gasparini, et al. Selective Activation of mGlu4 Metabotropic Glutamate Receptors Is Protective against Excitotoxic Neuronal Death J. Neurosci., September 1, 2000; 20(17): 6413 - 6420. [Abstract] [Full Text] [PDF]

				B. S. Meldrum Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology J. Nutr., April 1, 2000; 130(4): 1007 - 1007. [Abstract] [Full Text]

				J. W. Allen, S. A. Ivanova, L. Fan, M. G. Espey, A. S. Basile, and A. I. Faden Group II Metabotropic Glutamate Receptor Activation Attenuates Traumatic Neuronal Injury and Improves Neurological Recovery after Traumatic Brain Injury J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 112 - 120. [Abstract] [Full Text]

				V. Bruno, G. Battaglia, G. Casabona, A. Copani, F. Caciagli, and F. Nicoletti Neuroprotection by Glial Metabotropic Glutamate Receptors Is Mediated by Transforming Growth Factor-beta J. Neurosci., December 1, 1998; 18(23): 9594 - 9600. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help