Activation of Class II or III Metabotropic Glutamate Receptors Protects Cultured Cortical Neurons Against Excitotoxic Degeneration

  title={Activation of Class II or III Metabotropic Glutamate Receptors Protects Cultured Cortical Neurons Against Excitotoxic Degeneration},
  author={Valeria Bruno and Giuseppe Battaglia and Agata Copani and R. G. Giffard and Giuseppina Raciti and Rocco Raffaele and Haruhiko Shinozaki and Ferdinando Nicoletti},
  journal={European Journal of Neuroscience},
Trans‐1‐aminocyclopentane‐1,3‐dicarboxylic acid, a mixed agonist of all metabotropic glutamate receptor (mGluR) subtypes, is known to produce either neurotoxic or neuroprotective effects. We have therefore hypothesized that individual mGluR subtypes differentially affect neurodegenerative processes. Selective agonists of subtypes which belong to mGluR class II or III, such as (2s, 1′R,2′R,3′R)‐2‐(2,3‐dicarboxycyclopropyl)‐glycine (DCG‐IV) (specific for subtypes mGluR2 or 3) or L‐2‐amino‐4… 

Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures

The present data support the possibility that antagonizing group I mGluRs may be a useful strategy for attenuating excitotoxic neuronal death in certain disease states.

mGluR7‐like metabotropic glutamate receptors inhibit NMDA‐mediated excitotoxicity in cultured mouse cerebellar granule neurons

The present results add to the hypothesis that presynaptic mGLURs, probably mGluR7, may be the targets of drugs decreasing glutamate release and then neuronal death observed in some pathological situations.

Some Metabotropic Glutamate Receptor Ligands Reduce Kynurenate Synthesis in Rats by Intracellular Inhibition of Kynurenine Aminotransferase II

It is concluded that some mGluR ligands act intracellularly, inhibiting KAT II activity and therefore reducing kynurenate formation, and should be taken into consideration when novel mGlam glutamate receptor ligands are developed for the treatment of neurological and psychiatric diseases.

Selective Activation of mGlu4 Metabotropic Glutamate Receptors Is Protective against Excitotoxic Neuronal Death

Microdialysis studies showed that intrastriatal infusion of NMDA increased extracellular glutamate levels to a greater extent in −/− than in +/+ mice, supporting the hypothesis that the mGluR4 subtype is necessary for the maintenance of the homeostasis of extrace cellular glutamate levels.

An activity‐dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors

It is concluded that group I mGlu receptors are subjected to an activity‐dependent switch in regulating excitotoxic neuronal death and, therefore, the recent ‘history’ of these receptors is critical for the response to agonists or antagonists.

Neuroprotective activity of metabotropic glutamate receptor ligands.

A new generation of pharmacological agents allows a more stringent assessment of the role of individual mGluR-subtypes or groups of receptors in various nervous system disorders, including ischaemia-induced brain damage, traumatic brain injury, Huntington's and Parkinson's-like pathology or epilepsy.

Interaction Between A1 Adenosine and Class II Metabotropic Glutamate Receptors in the Regulation of Purine and Glutamate Release from Rat Hippocampal Slices

The evoked release of excitatory amino acids and purines is under an inhibitory control by A1 receptors and class II mGLURs, i.e., mGluR2 or 3, which appear to operate through a common transduction pathway.



A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord

DCG‐IV seems to reduce preferentially transmitter release from primary afferent nerve terminals of newborn rat motoneurones, and has the potential of providing further useful information on the physiological function of metabotropic glutamate receptors.

Attenuation of Excitatory Amino Acid Toxicity by Metabotropic Glutamate Receptor Agonists and Aniracetam in Primary Cultures of Cerebellar Granule Cells

It is demonstrated here that the concentration‐dependent stimulation of metabotropic glutamate receptor (mGluR) by the selective agonist trans‐1‐aminocyclopentane‐1, 3‐dicarboxylate or by quisqualate counteracts both glutamate‐ and kainate‐induced neurotoxicity in primary cultures of rat cerebellar granule cells.

Activation of the metabotropic glutamate receptor attenuates N-methyl-D-aspartate neurotoxicity in cortical cultures.

Concomitant activation of the ACPD receptor may serve as a protective mechanism against neurotoxicity that could be produced by brief intense NMDA receptor activation during normal or abnormal brain function.

Delayed rescue of N-methyl-D-aspartate receptor-mediated neuronal injury in cortical culture.

  • D. HartleyD. Choi
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1989
The present study explored the neuroprotective efficacy of delayed manipulations performed after completion of an excitotoxic insult by finding that cultured murine cortical neurons that would otherwise die after exposure to NMDA or glutamate could be rescued by the late addition of NMDA antagonists to the bathing medium.

Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4

The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family of at least five different subtypes, termed mGluR1-mGluR5. We studied the

Metabotropic glutamate receptors and neuronal toxicity.

A role for metabotropic receptors in the mechanism of neuronal degeneration has been suggested and the problem of toxic effects of quisqualate in hippocampal slices and cultured cortical neurons is addressed.

Intracellular messengers in the generation and degeneration of hippocampal neuroarchitecture

The results indicate that parallel intracellular messenger pathways that influence neurite outgrowth and cell survival are operative in hippocampal neurons; these messengers may play roles in the formation and modification of neuronal circuitry.

Positive feedback of glutamate exocytosis by metabotropic presynaptic receptor stimulation

The presence of a presynaptic glutamate receptor of the metabotropic type that mediates an enhancement of glutamate exocytosis in cerebrocortical nerve terminals is demonstrated and may have a physiological role in the maintenance of long-term potentiation.