Nitric oxide produced by non-motoneuron cells enhances rat embryonic motoneuron sensitivity to excitotoxins: comparison in mixed neuron/glia or purified cultures.

摘要: Abstract The present study compares the sensitivity to chronic exposure glutamate agonists of SMI-32-positive rat-derived embryonic motoneurons under both mixed neuron/glia and purified cultures. We found that in spite a trophic role glia on cultured motoneurons, cells are more sensitive excitotoxicity presence than culture, very likely through nitric oxide released by non-neuronal cells. rank order potency for inducing toxicity after 48 h incubation was AMPA>kainate>NMDA, with EC 50 : 0.43, 4.9 49 μM, respectively, culture 14, 32 135 μM effect NMDA dose-dependently potentiated glycine, similar two conditions. completely antagonized specific antagonists CNQX, BNQX MK801 Motoneurons were similarly immunoreactive NR1 GluR2 antibodies cultures, thus confirming calcium-impermeant AMPA receptor subtypes obligatory subunit receptors. kainate reduced addition 40 N -nitro- l -arginine or -NAME, which shifted 9 μM. By contrast, -NAME did not modify kainic acid These results suggest release enhances cells, direct activation ionotropic receptors is enough explain mechanism motoneuron degeneration occurring vivo amyotrophic lateral sclerosis (ALS).