Analysis of BMAA enantiomers in cycads, cyanobacteria, and mammals: in vivo formation and toxicity of d-BMAA
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Chronic dietary exposure to the cyanobacterial toxin β-N-methylamino-l-alanine (BMAA) triggers neuropathology in non-human primates, providing support for the theory that BMAA causes a fatal neurodegenerative illness among the indigenous Chamorro people of Guam. However, since there are two stereoisomers of BMAA, it is important to know if both can occur in nature, and if so, what role they might play in disease causation. As a first step, we analysed both BMAA enantiomers in cyanobacteria, cycads, and in mammals orally dosed with l-BMAA, to determine if enantiomeric changes could occur in vivo. BMAA in cyanobacteria and cycads was found only as the l-enantiomer. However, while the l-enantiomer in mammals was little changed after digestion, we detected a small pool of d-BMAA in the liver (12.5%) of mice and in the blood plasma of vervets (3.6%). Chiral analysis of cerebrospinal fluid of vervets and hindbrain of mice showed that the free BMAA in the central nervous system was the d-enantiomer. In vitro toxicity investigations with d-BMAA showed toxicity, mediated through AMPA rather than NMDA receptors. These findings raise important considerations concerning the neurotoxicity of BMAA and its relationship to neurodegenerative disease.
KeywordsChiral Enantiomer Neurodegenerative disease ALS/PDC Alzheimer’s Neurotoxicity
We acknowledge support from the John and Josephine Louis Foundation and the Deerbrook Charitable Trust. PBW acknowledges the use of the EPSRC UK National Mass Spectrometry Facility at Swansea University.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed and the appropriate institutional reviews and permissions were granted before the study was conducted.
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