TY - JOUR
AU - Prehn, J. H. M.
AB - Excitotoxic cell death is involved in many forms of acute and chronic neurodegeneration. We induced excitotoxic cell death in cultured rat hippocampal neurons by brief exposure to two selective glutamate receptor agonists with different neurotoxic potencies, N-methyl-d-aspartate (NMDA) and kainate (KA). Digital video imaging was performed during exposure to the agonists to monitor free radical production and changes in mitochondrial transmembrane potential, Ψm. Brief exposure to NMDA (10min) induced significant cell death in the hippocampal neurons reaching a maximum at a concentration of 300μM (57.2±2.6% cell death; P<0.001). In parallel imaging experiments we found that exposure to NMDA (300μM, 10min) induced a significant increase in superoxide production monitored with the oxidation-sensitive probe, hydroethidine (increase of 280±33% above baseline; P<0.001). Rhodamine-123-based imaging revealed a loss of Ψm in 70.1±10.1% of the hippocampal neurons during the exposure to NMDA. In contrast to NMDA, brief exposure to KA (10min) produced limited neurotoxicity reaching a maximum at a concentration of 100μM (10.2±4.0% cell death; P<0.05). Exposure to KA (100μM, 10min) also caused a significant increase in superoxide production. This increase, however, was significantly less pronounced than that produced by NMDA (increase of 94±17% above baseline; P<0.001 compared to controls or NMDA-exposed cultures). Moreover, rhodamine-123-based imaging revealed that KA (100μM) caused a collapse of Ψm in only 13.5±1.4% of the hippocampal neurons. In conclusion, the present study demonstrates that early changes in intracellular superoxide production and Ψm relate to neuronal survival outcome in excitotoxic cell death.
TI - Mitochondrial transmembrane potential and free radical production  in excitotoxic neurodegeneration
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
DO - 10.1007/PL00005173
DA - 1998-03-10
UR - https://www.deepdyve.com/lp/springer-journals/mitochondrial-transmembrane-potential-and-free-radical-production-in-DIBh0hffll
SP - 316
EP - 322
VL - 357
IS - 3
DP - DeepDyve
ER -