title: Excitotoxic potential of the cyanotoxin β-methyl-amino-L-alanine (BMAA) in primary human neurons.
abstract: The toxicity of the cyanobacterial modified amino acid, BMAA, has been described in rat, mouse and leech neurons. Particular emphasis has been placed on the potential ability of BMAA to induce neuronal damage via excitotoxic mechanisms. Here we present data indicating that the effects observed on lower organisms are also evident in a human model. Our data indicates that BMAA induces increased intracellular Ca²⁺ influx, DNA damage, mitochondrial activity, lactate dehydrogenase (LDH) release and generation of reactive oxygen species (ROS). The amelioration of LDH release in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 indicates that the neurotoxic effects of BMAA are mediated via NMDA receptor activation. Additionally, we have shown that BMAA induces the expression of neuronal nitric oxide synthase (nNOS) and caspase-3 indicating that it can stimulate apoptosis in human neurons, presumably via activation of NMDA receptors.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Chiu
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Gehringer
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Welch
authors.forename: Brett A
authors.initials: BA
authors.lastname: Neilan
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D000458:Cyanobacteria / Q000737:chemistry; D000087522:Cyanobacteria Toxins; D004249:DNA Damage / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; C001824:beta-N-methylamino-L-alanine; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; C505407:CASP3 protein, human; D053148:Caspase 3