Neurotoxicity of NAAG in vivo is sensitive to NMDA antagonists and mGluR II ligands.
N-Acetyl-aspartyl-glutamate (NAAG), an agonist at Group II metabotropic glutamate receptors (mGluR II), also activates the NMDA-type of ionotropic glutamate receptors and, at high micromolar concentrations, has previously been shown to induce neuronal cell death. In the present study we have morphologically quantified the neurotoxic action of intracerebroventricularly administered NAAG on the hippocampal formation and compared it to the action of the selective endogenous NMDA agonist quinolinic acid. Finally, we examined whether the action of NAAG can be modified by NMDA receptor antagonists and mGluR II ligands. NAAG-induced neurodegeneration was found to be less severe than that induced by quinolinate. It was prevented by inhibitors of NMDA receptors and also by an mGluR II agonist (DCG IV) but not by an mGluR II antagonist (EGlu).
Pliss
L
L
Department of Molecular Neurobiology, Institute of Physiology, Academy of Sciences, Prague 4, Czech Republic.
FitzGibbon
T
T
Balcar
V J
VJ
St'astný
F
F
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins; D010875:Pipecolic Acids / Q000494:pharmacology; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
D004151:Dipeptides; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D009498:Neurotoxins; D010875:Pipecolic Acids; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C027172:isospaglumic acid; C053672:selfotel; D016291:Dizocilpine Maleate; D017378:Quinolinic Acid