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

Banack, SA

Cox, GA

Cox, PA

Lobner, D

Metcalf, JS

Nunn, PB

Wyatt, PB

Amino Acids

English

J. S. Metcalf

Doug Lobner

Sandra Anne Banack

Gregory A. Cox

Peter B. Nunn

Peter B. Wyatt

Paul Alan Cox

Crossref

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

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.  Amino Acids 2017 Aug; 49(8):1427-1439

Metcalf, J S

Lobner, Doug

Banack, Sandra Anne

Cox, Gregory A

Nunn, Peter B

Wyatt, Peter B

Cox, Paul Alan

The Jackson Laboratory: The Mouseion at the JAXlibrary

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

Queen Mary Research Online

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

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

Metcalf, J. S.

Cox, Gregory A.

Nunn, Peter B.

Wyatt, Peter B.

epublications@Marquette

Analysis of BMAA Enantiomers in Cycads, Cyanobacteria, and Mammals: in vivo Formation and Toxicity of ᴅ-BMAA

https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/24600/1/Wyatt%20Analysis%20of%20BMAA%202017%20Accepted.pdf

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

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The Jackson Laboratory: The Mouseion at the JAXlibrary

Queen Mary Research Online

epublications@Marquette