The cyanobacterial amino acid β-N-methylamino-l-alanine perturbs the intermediary metabolism in neonatal rats

Engskog, Mikael K.R.; Karlsson, Oskar; Haglöf, Jakob; Elmsjö, Albert; Brittebo, Eva B.; Arvidsson, Torbjörn; Pettersson, Curt

doi:10.1016/j.tox.2013.07.010

Cited by 25 publications

(19 citation statements)

References 38 publications

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“…The present study revealed that BMAA perturbed metabolism pathways involving several neurotransmitters/neuromodulators and/or their precursors suggesting that BMAA-induced neurodegenerative effects in rodents and vervet monkeys may not only involve a potential misincorporation of this unusual amino acid into proteins but also other important functions such as neurotransmission. Furthermore, the observed BMAA-induced effects in human neuronal-like cells are in analogy with our previous study in BMAA-treated neonatal rodents showing perturbations of serum metabolites associated with changes in energy and amino acid metabolism (Engskog et al 2013). …”

Section: Discussionsupporting

confidence: 89%

“…However, BMAA is a developmental neurotoxin inducing long-term cognitive deficits as well as neurodegeneration, astrogliosis, and intracellular fibril formation in the hippocampus of adult rodents following neonatal exposure to BMAA (Karlsson et al 2009b, 2014). BMAA also induces behavioral changes in neonates and perturbs serum metabolites that are associated with changes in energy metabolism and amino acid metabolism (Karlsson et al 2009a; Engskog et al 2013). The neonatal rat model is so far the only animal model that displays significant biochemical and behavioral effects after a low short-term dose of BMAA.…”

Section: Introductionmentioning

confidence: 99%

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β-N-Methylamino-l-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling

et al. 2017

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β-Methylamino-l-alanine (BMAA) is a non-proteinogenic amino acid that induces long-term cognitive deficits, as well as an increased neurodegeneration and intracellular fibril formation in the hippocampus of adult rodents following short-time neonatal exposure and in vervet monkey brain following long-term exposure. It has also been proposed to be involved in the etiology of neurodegenerative disease in humans. The aim of this study was to identify metabolic effects not related to excitotoxicity or oxidative stress in human neuroblastoma SH-SY5Y cells. The effects of BMAA (50, 250, 1000 µM) for 24 h on cells differentiated with retinoic acid were studied. Samples were analyzed using LC–MS and NMR spectroscopy to detect altered intracellular polar metabolites. The analysis performed, followed by multivariate pattern recognition techniques, revealed significant perturbations in protein biosynthesis, amino acid metabolism pathways and citrate cycle. Of specific interest were the BMAA-induced alterations in alanine, aspartate and glutamate metabolism and as well as alterations in various neurotransmitters/neuromodulators such as GABA and taurine. The results indicate that BMAA can interfere with metabolic pathways involved in neurotransmission in human neuroblastoma cells.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

β-N-Methylamino-l-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling

et al. 2017

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“…Moreover, in a study by Engskog et al (2013) metabolic profiling of serum from BMAA-treated neonatal rats revealed significant alterations of the serum intermediates metabolites d-glucose, lactate, 3-hydroxybutyrate, acetate and creatine, which are associated with changes in energy metabolism and amino acid metabolism, demonstrating that BMAA induces systemic changes in energy metabolism and amino acid metabolism in neonates (Engskog et al, 2013).…”

Section: Acute and Repeated Toxicitymentioning

confidence: 99%

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Testai

Buratti

Funari

et al. 2016

EFS3

105

125

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This report presents the extensive literature search conducted on 1) the occurrence of different cyanotoxins in food matrices; 2) the analytical methods for their detection; 3) their toxicological profile; 3) the environmental factors affecting toxicity of cyanobacterial population and 4) the combined effects of mixtures of cyanotoxins and other chemicals. It also includes a review of guidelines values or health-alert levels for cyanotoxins in food (or drinking water) adopted world-wide. The methodological aspects and the queries used in the extensive literature search, the collection and screening of retrieved papers and the inventory are briefly described in the report; all details are available in 3 supplementary appendices to this report. The analysis of collected papers indicated that most of them are focused on a single microcystin (MC) variant (MC-LR) out of the almost 100 MC known. Many studies on occurrence are affected by limited quality, due to analytical drawbacks in the detection methods and were not considered in the exposure assessment. Toxicity studies useful for the derivation of health based reference values are few, being many of them carried out using i.p. injection, which is poorly representative of actual human exposure. In addition, those toxicological studies carried out with poorly characterised cyanobacterial extracts or focused on single parameters, using a single dose, devoted to elucidation of mechanism of action, reporting qualitative description of effects were not used for data extraction. The relevant exposure scenarios are also described, although being the available data on exposure very limited, no definite conclusion on the health risks for the exposed population could be drawn. However, the possibility of risky exposure is evidenced for fish and shell-fish consumers and for blue-green algae supplements (BGAS) as well in relation to MC contamination. Finally, many data gaps were identified. © European Food Safety Authority, 2016Key words: Cyanobacteria, cyanotoxins, occurrence, toxicity, exposure, risk assessment, data gaps. Question number: EFSA-Q-2015-00141Correspondence:sc.secretariat@efsa.europa.eu Cyanotoxins in foodThe present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.www.efsa.europa.eu/publications 2 EFSA Supporting publication 2016:EN-998NDisclaimer: The present document has been produced and adopted by the bodies identified above as author(s). This task has b...

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“…In addition L-BMAA is structurally very similar to glutamate (Cucchiaroni et al, 2010). It has been shown that the main mechanism by which L-BMAA causes neurotoxicity is by acting as an excitotoxin on glutamate receptors (L-BMAA is mixed glutamate receptor agonist) such as N-methyl-D-aspartic acid (NMDA) and calcium dependent a-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors (Chiu et al, 2012), which is believed to induce activation of calcium-dependent enzyme pathways (Bae et al, 2013) and oxidative stress by depletion of glutathione (Chiu et al, 2012;Engskog et al, 2013;Okle et al, 2013) as well as mitochondrial dysfunction . Nevertheless, the exact impact of non-protein amino acid L-BMAA on protein structure and function remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the mutagenic and genotoxic activity of cyanobacterial toxin beta-N-methyl-amino-L-alanine in Salmonella typhimurium

Novak

Hercog

Žegura

2016

Toxicon

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The cyanobacterial amino acid β-N-methylamino-l-alanine perturbs the intermediary metabolism in neonatal rats

Cited by 25 publications

References 38 publications

β-N-Methylamino-l-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling

β-N-Methylamino-l-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Assessment of the mutagenic and genotoxic activity of cyanobacterial toxin beta-N-methyl-amino-L-alanine in Salmonella typhimurium

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