Amino Acids

, Volume 49, Issue 8, pp 1427–1439 | Cite as

Analysis of BMAA enantiomers in cycads, cyanobacteria, and mammals: in vivo formation and toxicity of d-BMAA

  • J. S. Metcalf
  • Doug Lobner
  • Sandra Anne Banack
  • Gregory A. Cox
  • Peter B. Nunn
  • Peter B. Wyatt
  • Paul Alan Cox
Original Article

Abstract

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.

Keywords

Chiral Enantiomer Neurodegenerative disease ALS/PDC Alzheimer’s Neurotoxicity 

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Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  1. 1.Brain Chemistry LabsInstitute for EthnomedicineJacksonUSA
  2. 2.Department of Biomedical Sciences, College of Health SciencesMarquette UniversityMilwaukeeUSA
  3. 3.The Jackson LaboratoryBar HarborUSA
  4. 4.School of Pharmacy and Biomedical SciencesUniversity of PortsmouthPortsmouthUK
  5. 5.School of Biological and Chemical SciencesQueen Mary University of LondonLondonUK

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