Quinolinic acid protects rat cerebellar granule cells from glutamate-induced apoptosis.
The effects of quinolinic acid (QUIN) on glutamate-induced excitotoxicity were examined in primary cultures of rat cerebellar granule neurons. Exposing these neurons to QUIN (< or =2.5 mM) in the presence of glucose and Mg2+ had no effect on their viability. Although pretreating neurons with QUIN (10 microM) for 6 h did not reduce necrotic death induced by glutamate exposure in the absence of glucose and Mg2+, QUIN pretreatment significantly suppressed glutamate-induced apoptosis by 68% (as indicated by DNA fragmentation) in cultures containing glucose and Mg2+. Furthermore, the N-methyl-D-aspartate (NMDA) receptor antagonist AP-5 reversed QUIN-induced neuroprotection, while the non-NMDA antagonist CNQX had no effect. This study demonstrates that pathophysiologically relevant concentrations of QUIN can protect neurons from apoptosis mediated via the NMDA receptor.
Sei
Y
Y
Department of Anesthesiology, The Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA. Ysei@mx3.usuhs.mil
Fossom
L
L
Goping
G
G
Skolnick
P
P
Basile
A S
AS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D016015:Logistic Models; D016202:N-Methylaspartate / Q000494:pharmacology; D009336:Necrosis; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D016202:N-Methylaspartate; D017378:Quinolinic Acid