Abstract
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 (∼ 30 μM) 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 [Ca2+]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.
Original language | English (US) |
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Pages (from-to) | 244-252 |
Number of pages | 9 |
Journal | Experimental Neurology |
Volume | 201 |
Issue number | 1 |
DOIs | |
State | Published - Sep 1 2006 |
Keywords
- ALS
- ALS-PDC
- ALS/PDC
- AMPA
- Amyotrophic lateral sclerosis
- Ca
- Cell culture
- Cycad
- Glutamate
- Guam
- Motor neuron
- ROS
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience