Cyanobacterial Neurotoxin BMAA and Mercury in Sharks

Hammerschlag, Neil; Da, Davis; Mondo, Kiyo; Seely, Matthew S.; Murch, Susan J.; Glover, W. Broc; Divoll, Timothy J.; Evers, David C.; Mash, Deborah C.

doi:10.3390/toxins8080238

Cited by 36 publications

(18 citation statements)

References 46 publications

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“…Among marine taxa, the BMAA content appears to be much higher in sharks to date. Total BMAA concentrations between 19.2 and 33.15 mg kg −1 FW were reported in fins and muscle of four shark species [ 59 ]. From this study, we only considered data of quantification performed by ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and not the one acquired by liquid chromatography with fluorescence detection (HPLC-FLD), the latter technique being less specific.…”

Section: Resultsmentioning

confidence: 99%

“…The same trend is observed for marine fish in which either no BMAA or a maximum of 0.02 mg kg −1 FW of total BMAA is reported [ 50 , 54 ]. Although data mainly originate from a B graded study, it is noteworthy to mention the high BMAA contents (up to 33.15 mg kg −1 FW) reported in shark fins [ 59 ]. Moreover, a study graded A reported BMAA concentrations from 74.8 to 352.2 mg kg −1 DW in 15 out of 16 analyzed dietary supplements containing shark cartilage [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans

Lance

Arnich

Maignien

et al. 2018

Toxins

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The neurotoxin β-N-methylamino-l-alanine (BMAA), a non-protein amino acid produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been suggested to play a role as an environmental factor in the neurodegenerative disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC). The ubiquitous presence of BMAA in aquatic environments and organisms along the food chain potentially makes it public health concerns. However, the BMAA-associated human health risk remains difficult to rigorously assess due to analytical challenges associated with the detection and quantification of BMAA and its natural isomers, 2,4-diamino butyric acid (DAB), β-amino-N-methyl-alanine (BAMA) and N-(2-aminoethyl) glycine (AEG). This systematic review, reporting the current knowledge on the presence of BMAA and isomers in aquatic environments and human food sources, was based on a selection and a score numbering of the scientific literature according to various qualitative and quantitative criteria concerning the chemical analytical methods used. Results from the best-graded studies show that marine bivalves are to date the matrix containing the higher amount of BMAA, far more than most fish muscles, but with an exception for shark cartilage. This review discusses the available data in terms of their use for human health risk assessment and identifies knowledge gaps requiring further investigations.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans

Lance

Arnich

Maignien

et al. 2018

Toxins

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“…One emerging toxin is β- N -methylamino- l -alanine (BMAA), a non-protein amino acid produced by cyanobacteria that has been linked to neurodegenerative disease, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) [ 6 , 7 , 8 ]. BMAA can biomagnify in marine and terrestrial food chains, where it can bioaccumulate in marine apex predators and humans [ 6 , 8 , 9 , 10 , 11 , 12 ]. Exposure to BMAA causes excitotoxicity in neurons, glial activation, and tangled proteins in the brain [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure

Garamszegi

Banack

et al. 2021

Toxins

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Dolphins are well-regarded sentinels for toxin exposure and can bioaccumulate a cyanotoxin called β-N-methylamino-l-alanine (BMAA) that has been linked to human neurodegenerative disease. The same dolphins also possessed hallmarks of Alzheimer’s disease (AD), suggesting a possible association between toxin exposure and neuropathology. However, the mechanisms of neurodegeneration in dolphins and the impact cyanotoxins have on these processes are unknown. Here, we evaluate BMAA exposure by investigating transcription signatures using PCR for dolphin genes homologous to those implicated in AD and related dementias: APP, PSEN1, PSEN2, MAPT, GRN, TARDBP, and C9orf72. Immunohistochemistry and Sevier Münger silver staining were used to validate neuropathology. Methylmercury (MeHg), a synergistic neurotoxicant with BMAA, was also measured using PT-GC-AFS. We report that dolphins have up to a three-fold increase in gene transcription related to Aβ+ plaques, neurofibrillary tangles, neuritic plaques, and TDP-43+ intracytoplasmic inclusions. The upregulation of gene transcription in our dolphin cohort paralleled increasing BMAA concentration. In addition, dolphins with BMAA exposures equivalent to those reported in AD patients displayed up to a 14-fold increase in AD-type neuropathology. MeHg was detected (0.16–0.41 μg/g) and toxicity associated with exposure was also observed in the brain. These results demonstrate that dolphins develop neuropathology associated with AD and exposure to BMAA and MeHg may augment these processes.

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“…(1) The concentration of BMAA in flying foxes is indeed high relative to BMAA concentrations in most organisms from other worldwide ecosystems (e.g., Jonasson et al 2010;Brand et al 2010;Christensen et al 2012;Mondo et al 2012Mondo et al , 2014Field et al 2013;Masseret et al 2013;Al-Sammak et al 2014;Banack et al 2014Banack et al , 2015Jiang et al 2014;Réveillon et al 2016;Hammerschlag et al 2016;Scott et al 2018;Lance et al 2018).…”

Section: Misrepresentation Of the Flying Fox Hypothesismentioning

confidence: 99%

“…Follow-up studies should include even lower doses and oral exposure to identify the no observed adverse effect level (NOAEL) and further elucidate underlying mechanisms. Furthermore, Chernoff et al (2017) fail to consider co-exposure issues, e.g., individuals exposed to cyanobacterial blooms likely face more than one cyanotoxin, or in the case of simultaneous red tides and cyanobacterial blooms, multiple cyanotoxins plus brevetoxins (Metcalf et al 2020) or even methyl mercury, whose toxicity BMAA potentiates in vitro (Rush et al 2012;Mondo et al 2014;Hammerschlag et al 2016). Also, the magnitude of toxicity may be different among BMAA isomers at different ratios, e.g., BMAA is more toxic at lower concentrations than N-(2-aminoethyl)glycine (AEG) to brine shrimp (Metcalf et al 2015) while in vitro AEG is much more neurotoxic (Schneider et al 2020).…”

Section: Dosing Paradigmsmentioning

confidence: 99%

Is Exposure to BMAA a Risk Factor for Neurodegenerative Diseases? A Response to a Critical Review of the BMAA Hypothesis

Dunlop

et al. 2021

Neurotox Res

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In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to β-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer’s disease, Parkinson’s disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review’s title which incorrectly refers to BMAA as a “non-essential” amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they are fit-for-purpose. Although there remain gaps in the literature, an increasingly large body of data from multiple independent labs using orthogonal methods provides increasing evidence that chronic exposure to BMAA may be a risk factor for neurological illness.

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Cyanobacterial Neurotoxin BMAA and Mercury in Sharks

Cited by 36 publications

References 46 publications

Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans

Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans

BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure

Is Exposure to BMAA a Risk Factor for Neurodegenerative Diseases? A Response to a Critical Review of the BMAA Hypothesis

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