Quinolinic acid promotes the biochemical differentiation of cerebellar granule neurons

The possible involvement of quinolinic acid in the biochemical differentiation of cultured glutamatergic cerebellar granule neurons was studied in terms of the activity of phosphate-activated glutaminase (GLNase) and aspartate aminotransferase (ASP-AT). Treatment with quinolinate elevated the specific activity of GLNase and amount of protein per culture dish in a dose-dependent manner. The half maximal effect was obtained at about 0.5 mM quinolinate, whereas the maximum concentration, which produced about a 2.3-fold increase in GLNase activity, was about 2 mM. Quinolinate, like N-methyl-D-aspartate (NMDA), had no significant effects on the activities of ASP-AT and lactate dehydrogenase enzymes. The increases in the activity of GLNase and amount of protein were completely blocked by the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid. The result would indicate that, (a) contrary to an earlier proposal, ASP-AT does not appear to be a good marker for studying dynamic responses of glutamatergic neurons, and (b) the trophic effect of quinolinic acid on the development of cerebellar granule neurons is mediated by selective activation of NMDA subtype excitatory amino acid receptors.