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 (less than or equal to 2.5 mM) in the presence of glucose and Mg2+ had no effect on their viability. Although pretreating neurons with QUIN (10 mu M) 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 M-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. (C) 1998 Elsevier Science Ireland Ltd.