2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline has been researched along with Plant-Poisoning* in 1 studies
1 other study(ies) available for 2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and Plant-Poisoning
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BMAA selectively injures motor neurons via AMPA/kainate receptor activation.
The toxin beta-methylamino-l-alanine (BMAA) has been proposed to contribute to amyotrophic lateral sclerosis-Parkinsonism Dementia Complex of Guam (ALS/PDC) based on its ability to induce a similar disease phenotype in primates and its presence in cycad seeds, which constituted a dietary item in afflicted populations. Concerns about the apparent low potency of this toxin in relation to estimated levels of human ingestion led to a slowing of BMAA research. However, recent reports identifying potential new routes of exposure compel a re-examination of the BMAA/cycad hypothesis. BMAA was found to induce selective motor neuron (MN) loss in dissociated mixed spinal cord cultures at concentrations ( approximately 30 muM) significantly lower than those previously found to induce widespread neuronal degeneration. The glutamate receptor antagonist NBQX prevented BMAA-induced death, implicating excitotoxic activation of AMPA/kainate receptors. Using microfluorimetric techniques, we further found that BMAA induced preferential [Ca(2+)](i) rises and selective reactive oxygen species (ROS) generation in MNs with minimal effect on other spinal neurons. Cycad seed extracts also triggered preferential AMPA/kainate-receptor-dependent MN injury, consistent with the idea that BMAA is a crucial toxic component in this plant. Present findings support the hypothesis that BMAA may contribute to the selective MN loss in ALS/PDC. Topics: Amino Acids, Diamino; Amyotrophic Lateral Sclerosis; Animals; Calcium; Cell Survival; Cells, Cultured; Cyanobacteria Toxins; Cycas; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Humans; Mice; Motor Neurons; Neurotoxins; Plant Extracts; Plant Poisoning; Quinoxalines; Reactive Oxygen Species; Receptors, AMPA; Receptors, Kainic Acid; Seeds; Spinal Cord | 2006 |