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.
Liu
Xiao Qian
XQ
Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin 53233, USA.
Rush
Travis
T
Ciske
Jennifer
J
Lobner
Doug
D
D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D020665:Septum of Brain / Q000166:cytology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C001824:beta-N-methylamino-L-alanine; D045022:Lactate Dehydrogenases; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase