 |
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 Nicoletti1, 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,1 R,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]
|
|
|
|
|
