Animal models of BMAA neurotoxicity: a critical review.
Of all the molecules reported to have toxicological effects, BMAA (beta-methylamino alanine) stands out as having the most checkered past. In the late 1960's it was reported to be a toxic component of the cycad flour consumed by Chamorros on Guam which caused the high incidence of amyotrophic lateral sclerosis (ALS) in Guam, that was associated with a Parkinson's disease-like dementia complex (ALS-PDC). However, because ALS-PDC is a slow onset disease, manifesting itself as long as 30 years following exposure to the putative neurotoxin, and only acute toxic effects of BMAA were observed in animal studies, interest in BMAA waned. A seminal study by Spencer et al., in 1987 showing neurological impairments with long-term BMAA-fed monkeys revived the hypothesis that BMAA could cause ALS-PDC. However, the amounts of BMAA used in that study were viewed as being the equivalent of a person consuming their body weight of cycad flour every day. Again, the BMAA hypothesis was discarded. Recently a third iteration of the BMAA hypothesis has been proposed. It is based on the discovery of a novel dietary source of BMAA via biomagnification of BMAA in flying foxes, once consumed in great amounts by Chamorros. Also, reports that BMAA can be incorporated into plant and animal proteins, a heretofore unrecognized dietary source of BMAA, further solidified this new hypothesis. However, once again this hypothesis has its detractors and it remains controversial. This manuscript critically evaluates in vivo studies directed at establishing an animal model of BMAA-induced ALS-PDC and their implications for this hypothesis.
Karamyan
Vardan T
VT
Department of Pharmacology, School of Pharmacy, University of Mississippi, MS 38677, USA.
Speth
Robert C
RC
D000599:Amino Acids, Diamino / Q000378:metabolism / Q000633:toxicity*; D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects*; D000087522:Cyanobacteria Toxins; D004195:Disease Models, Animal; D004781:Environmental Exposure; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000633:toxicity*; D020387:Food Chain; D005506:Food Contamination; D006141:Guam; D008460:Meat / Q000032:analysis; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D010945:Plants, Edible / Q000737:chemistry / Q000378:metabolism
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine