Selective death of cholinergic neurons induced by beta-methylamino-L-alanine

Beta-N-methylamino-L-alanine (BMAA) is a nonprotein amino acid that may be involved in neurodegenerative diseases. It is produced by a large variety of cyanobacteria and is found at high levels in the brains of Alzheimer's disease and amyotrophic lateral sclerosis patients. Although BMAA is clearly a neurotoxin, previous studies using cortical cultures indicated that millimolar concentrations were required to cause toxicity. We tested the toxicity of BMAA in septal cultures containing cholinergic neurons and mesencephalic cultures containing dopaminergic neurons. We found that cholinergic, but not dopaminergic, neurons were selectively vulnerable to BMAA toxicity, with toxicity occurring at 30 microM. The toxicity of BMAA to total septal neurons involved activation of N-methyl D-aspartate receptors, whereas the death of cholinergic neurons was mediated by AMPA/kainate receptors.