BMAA selectively injures motor neurons via AMPA/kainate receptor activation

Shyam Rao, Sandra Anne Banack, Paul Alan Cox, John H. Weiss

Research output: Contribution to journalArticle

170 Scopus citations

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 languageEnglish (US)
Pages (from-to)244-252
Number of pages9
JournalExperimental Neurology
Volume201
Issue number1
DOIs
StatePublished - 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

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