Glutaric acid (GA) has been implicated in the mechanism of neurodegeneration in glutaric aciduria type I. In the present study, the potential cytotoxic effects of GA (0.1 similar to 50 mM for 24 similar to 96 h) were examined in cultured primary rat striatal neurons. Results showed increase in the number of cells labeled by annexin-V or with apoptotic features shown by Hoechst/PI staining and transmission electron microscopy (TEM) and upregulation of the expression of mRNA as well as the active protein fragments caspase 3, suggesting involvement of the caspase 3-dependent apoptotic pathway inGA-induced striatal neuronal death. This effect was in part suppressed by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 but not the alpha-amino-3-hydroxy-5-methylisoxazole4- propionic acid (AMPA) antagonist 6-cyano-7-nitroquinoxalone-2,3-dione (CNQX). Thus, GA may trigger neuronal damage partially through apoptotic pathway and via activation of NMDA receptors in cultured primary striatal neurons.