Beta-N-methylamino-L-alanine. Chronic oral administration is not neurotoxic to mice.
Repeated dietary consumption of the neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA), found in the seeds of Cycas circinalis, has been postulated as causing both amyotrophic lateral sclerosis (ALS) and the parkinsonism-dementia syndrome (PD) that were formerly very prevalent among the indigenous people of the Marianas Islands. Cynomolgus monkeys fed BMAA have been reported to develop behavioral and neuropathological changes like those found in human ALS. We gave large amounts of BMAA, totaling 15.5 g/kg of the L-isomer, by gavage to mice over 11 weeks without observing any behavioral abnormalities. When killed, these animals showed none of the neurochemical or neuropathological changes that would be expected in ALS or Parkinson's disease. Their striatal dopamine contents were normal, and there were no reductions in the contents of glutamate and aspartate in cerebral cortex like those encountered in sporadic human ALS. The results of this experiment do not support chronic ingestion of BMAA as the causative factor for Guamanian ALS or PD.
Perry
T L
TL
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Bergeron
C
C
Biro
A J
AJ
Hansen
S
S
D000284:Administration, Oral; D000596:Amino Acids / Q000378:metabolism; D000599:Amino Acids, Diamino / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000087522:Cyanobacteria Toxins; D004298:Dopamine / Q000378:metabolism; D005260:Female; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000596:Amino Acids; D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine; D004298:Dopamine