KAINATE INDUCES APOPTOSIS IN NEURONS

Growing evidence suggests that non-N-methyl-D-aspartate receptor activ ation may contribute to neuronal death in both acute and chronic neuro logical diseases. The intracellular processes that mediate this form o f neuronal death are poorly understood. We have previously characteriz ed a model of kainate neurotoxicity using cerebellar granule cell neur ons in vitro and we sought to determine the mechanism of kainate-induc ed neuronal degeneration. We found DNA laddering by agarose gel electr ophoresis, cellular DNA fragmentation by in situ end iabeling of DNA, and chromatin condensation using a fluorescent DNA intercalating dye, in cerebellar granule cells following exposure to kainate (100 mu M). Aurintricarboxylic acid protected cerebellar granule cells from kainat e-induced death. While the morphological and biochemical features of n euronal death induced by kainate resembled low-K+-induced apoptosis in cerebellar granule cells, the time interval from the institution of t he death-promoting condition to neuronal death was briefer with kainat e and did not require new protein or RNA synthesis. These results demo nstrate that kainate receptor activation can induce transcription-inde pendent apoptosis in neurons. This in vitro model should be useful in identifying the intracellular pathways that link kainate receptor acti vation with apoptosis. Copyright (C) 1996 IBRO.