New Typical Vector of Neurotoxin β-N-Methylamino-l-Alanine (BMAA) in the Marine Benthic Ecosystem

Abstract

The neurotoxin β-N-methylamino-l-alanine (BMAA) has been identified as an environmental factor triggering neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD). We investigated the possible vectors of BMAA and its isomers 2,4-diaminobutyric acid (DAB) and N-2(aminoethyl)glycine (AEG) in marine mollusks collected from the Chinese coast. Sixty-eight samples of marine mollusks were collected along the Chinese coast in 2016, and were analyzed by an HILIC-MS/MS (hydrophilic interaction liquid chromatography with tandem quadrupole mass spectrometer) method without derivatization. BMAA was detected in a total of five samples from three species: Neverita didyma, Solen strictus, and Mytilus coruscus. The top three concentrations of free-form BMAA (0.99~3.97 μg·g−1 wet weight) were detected in N. didyma. DAB was universally detected in most of the mollusk samples (53/68) with no species-specific or regional differences (0.051~2.65 μg·g−1 wet weight). No AEG was detected in any mollusk samples tested here. The results indicate that the gastropod N. didyma might be an important vector of the neurotoxin BMAA in the Chinese marine ecosystem. The neurotoxin DAB was universally present in marine bivalve and gastropod mollusks. Since N. didyma is consumed by humans, we suggest that the origin and risk of BMAA and DAB toxins in the marine ecosystem should be further investigated in the future.

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

“…In China, 68 samples from 29 species originating from aquaculture and bought at local markets of several towns were analyzed in a study graded B [ 58 ]. The presence of free BMAA in 5 of the 68 edible mollusks from three marine species was reported: one mussel ( Mytilus coruscus 0.45 mg kg −1 FW) sample out of nine, one razor clam ( Solen strictus 0.66 mg kg −1 FW) out of one, and three gastropods ( Neverita didyma up to 3.97 mg kg −1 FW) out of five analyzed.…”

“…To assess health risk associated with BMAA-containing food, it is of great importance that data includes all the BMAA fractions (free, soluble or precipitated-bound, or total). Most of the studies we graded A and B report the total BMAA content in edible organisms, few of them [ 23 , 24 , 43 , 44 , 54 , 58 ] report both the total and free BMAA contents, or both the total soluble and free BMAA contents [ 23 , 24 , 43 , 44 , 54 , 58 ]. In these last studies, the total soluble BMAA content far exceeds that of free BMAA (e.g., maximum of 2.45 mg total BMAA kg −1 FW against 0.2 mg free BMAA kg −1 FW in mussels) [ 23 , 24 ].…”

“…The authors also mentioned the possibility of a chelation with metals or carbamate formation that can lead to different forms of bound BMAA in biological matrix. The amount of amino acids (Arg, Asp, Glu, Leu, Lys, Ser, Thr, Ile and Met) measured in muscle of a marine snail was shown to decrease concomitantly with the increase of the free BMAA content, suggesting that BMAA is not incorporated into proteins but may affect their synthesis [ 58 ]. Moreover, it was recently demonstrated that the slight toxicity of BMAA on human cell lines was not the result of its misincorporation into proteins, as no BMAA was detected in purified protein extracts [ 11 ].…”

“…Similar observations were reported in 100% of the samples collected in three Chinese lakes [ 49 ]. Interestingly, in China, free BMAA was detected in five out of 68 edible species, whereas free DAB was detected in 53 of them, at similar concentrations between species and prospected areas [ 58 ]. Identically, the total BMAA and AEG contents in marine bivalves showed seasonal variations with an increase in summer and autumn (years 2009, 2013 and 2014) that was concomitant to the increased filtration activity and phytoplanktonic densities, suggesting an environmental and seasonal origin of those amino acids and a contamination by a trophic pathway.…”

Marine Neurotoxins: a Double-edged Sword in Food Industry and Brain Research

“…BMAA has been hypothesized to trigger the pathogenesis of neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's disease (AD). Extensive in vitro experiments have demonstrated that the neurotoxicity of BMAA for neurons is a result of multiple mechanisms including action on glutamate receptors to induce oxidative stress in the neuron by depleting glutathione and generating a cytotoxic DNA damaging alkylating agent [60,61] . Study with vervets showed that BMAA may trigger neurodegenerative disease such as Alzheimer's Disease as a result of gene/environment interaction, thus it could became a useful tool for studying of neurodegenerative disease [62,63] .…”