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Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure
Stockholm University, Faculty of Science, Department of Botany.
Stockholm University, Faculty of Science, Department of Botany.
Stockholm University, Faculty of Science, Department of Botany.
Stockholm University, Faculty of Science, Department of Analytical Chemistry. Charles University Prague, Czech Republic .
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2010 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 20, 9252-9257 p.Article in journal (Refereed) Published
Abstract [en]

beta-methylamino-L-alanine (BMAA), a neurotoxic nonprotein amino acid produced by most cyanobacteria, has been proposed to be the causative agent of devastating neurodegenerative diseases on the island of Guam in the Pacific Ocean. Because cyanobacteria are widespread globally, we hypothesized that BMAA might occur and bioaccumulate in other ecosystems. Here we demonstrate, based on a recently developed extraction and HPLC-MS/MS method and long-term monitoring of BMAA in cyanobacterial populations of a temperate aquatic ecosystem (Baltic Sea, 2007-2008), that BMAA is biosynthesized by cyanobacterial genera dominating the massive surface blooms of this water body. BMAA also was found at higher concentrations in organisms of higher trophic levels that directly or indirectly feed on cyanobacteria, such as zooplankton and various vertebrates (fish) and invertebrates (mussels, oysters). Pelagic and benthic fish species used for human consumption were included. The highest BMAA levels were detected in the muscle and brain of bottom-dwelling fishes. The discovery of regular biosynthesis of the neurotoxin BMAA in a large temperate aquatic ecosystem combined with its possible transfer and bioaccumulation within major food webs, some ending in human consumption, is alarming and requires attention.

Place, publisher, year, edition, pages
2010. Vol. 107, no 20, 9252-9257 p.
Keyword [en]
beta-methylamino-L-alanine, Baltic Sea, cyanobacteria, liquid chromatography/mass spectrometry, bioaccumulation
National Category
Biological Sciences
Research subject
Plant Physiology
Identifiers
URN: urn:nbn:se:su:diva-50529DOI: 10.1073/pnas.0914417107ISI: 000277822600043OAI: oai:DiVA.org:su-50529DiVA: diva2:381619
Note

authorCount :8

Available from: 2010-12-28 Created: 2010-12-28 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Mass Spectrometry of Biologically Active Small Molecules: Focusing on polyphenols, alkaloids and amino acids
Open this publication in new window or tab >>Mass Spectrometry of Biologically Active Small Molecules: Focusing on polyphenols, alkaloids and amino acids
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The foci of this dissertation are on advanced liquid chromatography (LC) separation and mass spectrometry (MS) techniques for the analysis of small bioactive molecules. In addition to discussing general aspects of such techniques the results from analyses of polyphenols (PPs), alkaloids and amino acids published in five appended studies are presented and discussed. High efficiency and well understood principles make LC the method of choice for separating analytes in many kinds of scientific investigations. Moreover, when LC is coupled to an MS instrument, analytes are separated in two stages: firstly they are separated and pre-concentrated in narrow bands using LC and then separated according to their mass-to-charge (m/z) ratios in the MS instrument. Some MS instruments can provide highly accurate molecular weight measurements and mass resolution allowing identification of unknown compounds based purely on MS data, thus making prior separation unnecessary. However, prior separation is essential for analyzing substances in most complex matrices – especially useful is the ultra-high performance LC (UHPLC). The advantages of using UHPLC rather than HPLC for the analysis of PPs in tea and wine were evaluated in one of the studies this thesis is based upon. The phenolic composition of red wine was also examined, using a novel LDI technique, following solid phase extraction (SPE). A class of small aromatic molecules (medicinally important alkaloids) also proved to be amenable to straightforward analysis, by thin layer chromatography (TLC) work-up followed by LDI-MS. Finally, a LC-MS method for monitoring neurotoxins (β-N-methyl-amino-L-alanine and 2,3-diaminobutyric acid) in complex biological matrices was developed and applied. Overall, the studies show that careful attention to the physicochemical properties of analytes can provide insights that can greatly facilitate the development of alternative methods to analyze them, e.g. by LDI.

Place, publisher, year, edition, pages
Stockholm: Department of Analytic Chemistry, Stockholm University, 2010. 61 p.
Keyword
LC-MS, LDI, Mass spectrometry, HPLC, UHPLC, polyphenols, phenolic acids, BMAA
National Category
Analytical Chemistry Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-33233 (URN)978-91-7155-982-1 (ISBN)
Public defence
2010-01-29, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: In press. Paper 5: Manuscript.

Available from: 2010-01-07 Created: 2009-12-21 Last updated: 2015-06-08Bibliographically approved
2. Detection, transfer and role of an environmentally spread neurotoxin (BMAA) with focus on cyanobacteria and the Baltic Sea region
Open this publication in new window or tab >>Detection, transfer and role of an environmentally spread neurotoxin (BMAA) with focus on cyanobacteria and the Baltic Sea region
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

β-N-methylamino-L-alanine (BMAA) is one of the more recently discovered bioactive compounds produced by cyanobacteria. BMAA is a non-protein amino acid reported present in human brain tissues of patients deceased from a neurodegenerative disease, such as Alzheimer´s disease or amyotrophic lateral sclerosis (ALS). This observation in combination with its neurotoxic effects in eukaryotes (in vivo and in vitro) and its potential to incorporate into (human) proteins, causing protein aggregation, suggests BMAA as a possible causative environmental agent for neurodegenerative diseases. Due to the ubiquitous nature of cyanobacteria with a wide occurrence in both aquatic and terrestrial environments, BMAA could be globally spread. Hence, investigations of a possible coupling between BMAA and neurodegeneration are urgently needed as well as to identify sources of BMAA in Nature.

The aim of this thesis was to examine the potential occurrence of BMAA in bloom forming cyanobacteria of the Baltic Sea and its possible transfer to other organisms of this ecosystem. Of importance was also to reveal any likely routes for human BMAA exposure in the Baltic Sea region and to further investigate BMAA as a triggering agent for neurodegenerative diseases. Acknowledged difficulties of analysing BMAA in biological samples also inferred method development as part of the experimental studies. Investigating the role of BMAA in its producers was another purpose of the thesis, which may be crucial for future management of BMAA-producing cyanobacteria.

By screening natural populations of the major filamentous bloom forming cyanobacteria of the Baltic Sea, we discovered the presence of BMAA throughout the entire summer season of two consecutive years, using a highly specific analytical method (liquid chromatography-tandem mass spectrometry; LC-MS/MS). BMAA was found to bioaccumulate in zooplankton and fish, as well as in mussels and oysters from the Swedish west coast. To improve the understanding of BMAA analyses in natural samples, the formation of carbamate adducts in the presence of bicarbonate was examined. Using two derivatization techniques in combination with LC-MS/MS, we could show that BMAA detection was not hindered by carbamate formation. Exogenously added BMAA inhibited nitrogen fixation in the model cyanobacterium Nostoc sp. PCC 7120, which was also hampered in growth and displayed signs of nitrogen starvation. Finally, BMAA was detected in cerebrospinal fluid in three of 25 Swedish test individuals, and represents the first confirmation of BMAA in the human central nervous system using LC-MS/MS as the primary analytical method. However, the association of BMAA to neurodegenerative diseases could not be verified as BMAA was present in both control individuals (two) and in one ALS-patient. Nevertheless, the finding of a known neurotoxic compound in the human central nervous system is alarming and potential consequences should be investigated.

The discovery of the neurotoxic compound BMAA in Baltic Sea organisms, and in the central nervous system of humans potentially consuming fish from this ecosystem is concerning and warrants continued investigations of BMAA occurrence and human exposure. Further knowledge on the function and regulation of BMAA may help in developing strategies aiming to minimise human exposure.

Place, publisher, year, edition, pages
Stockholm: Department of Ecology, Environment and Plant Sciences, Stockholm University, 2015. 85 p.
Keyword
β-N-methylamino-L-alanine, BMAA, cyanobacteria, Baltic Sea, blooms, neurotoxin, neurodegenerative diseases, amyotrophic lateral sclerosis, ALS, nitrogenase, nitrogen fixation
National Category
Biological Sciences
Research subject
Plant Physiology
Identifiers
urn:nbn:se:su:diva-118882 (URN)978-91-7649-142-3 (ISBN)
Public defence
2015-09-10, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

Available from: 2015-08-19 Created: 2015-07-16 Last updated: 2015-08-21Bibliographically approved

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Jonasson, SaraEriksson, JohanBerntzon, LottaIlag, Leopold L.Rasmussen, UllaBergman, Birgitta
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