DETECTION OF BMAA IN THE HUMAN CENTRAL NERVOUS SYSTEM

被引:46
作者
Berntzon, L. [1 ]
Ronnevi, L. O. [2 ]
Bergman, B. [1 ]
Eriksson, J. [1 ]
机构
[1] Stockholm Univ, Dept Ecol Environm & Plant Sci, SE-10691 Stockholm, Sweden
[2] Karolinska Inst, Dept Clin Neurosci, SE-17176 Stockholm, Sweden
关键词
neurotoxin; BMAA; neurodegeneration; ALS; CSF; blood; METHYLAMINO-L-ALANINE; AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSON-DEMENTIA COMPLEX; CYANOBACTERIAL NEUROTOXIN; AMINO-ACID; NEURODEGENERATIVE DISEASE; MASS-SPECTROMETRY; CHAMORRO PEOPLE; BRAIN; PROTEIN;
D O I
10.1016/j.neuroscience.2015.02.032
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Amyotrophic lateral sclerosis (ALS) is an extremely devastating neurodegenerative disease with an obscure etiology. The amino acid beta-N-methyl-L-alanine (BMAA) produced by globally widespread phytoplankton has been implicated in the etiology of human motor neuron diseases. BMAA was recently proven to be present in Baltic Sea food webs, ranging from plankton to larger Baltic Sea organisms, some serving as important food items (fish) for humans. To test whether exposure to BMAA in a Baltic Sea setting is reflected in humans, blood and cerebrospinal fluid (CSF) from individuals suffering from ALS were analyzed, together with sex- and age-matched individuals not inflicted with ALS. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and multiple reaction monitoring (MRM), in conjunction with diagnostic transitions revealed BMAA in three (12%) of the totally 25 Swedish individuals tested, with no preference for those suffering from ALS. The three BMAA-positive samples were all retrieved from the CSF, while BMAA was not detected in the blood. The data show that BMAA, potentially originating from Baltic Sea phytoplankton, may reach the human central nervous system, but does not lend support to the notion that BMAA is resident specifically in ALS-patients. However, while dietary exposure to BMAA may be intermittent and, if so, difficult to detect, our data provide the first demonstration of BMAA in the central nervous system of human individuals ante mortem quantified with UHPLC-MS/MS, and therefore calls for extended research efforts. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of IBRO.
引用
收藏
页码:137 / 147
页数:11
相关论文
共 60 条
  • [1] Co-occurrence of the Cyanotoxins BMAA, DABA and Anatoxin-a in Nebraska Reservoirs, Fish, and Aquatic Plants
    Al-Sammak, Maitham Ahmed
    Hoagland, Kyle D.
    Cassada, David
    Snow, Daniel D.
    [J]. TOXINS, 2014, 6 (02) : 488 - 508
  • [2] Distinguishing the cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) from other diamino acids
    Banack, S. A.
    Metcalf, J. S.
    Spacil, Z.
    Downing, T. G.
    Downing, S.
    Long, A.
    Nunn, P. B.
    Cox, P. A.
    [J]. TOXICON, 2011, 57 (05) : 730 - 738
  • [3] Neurotoxic flying foxes as dietary items for the Chamorro people, Marianas Islands
    Banack, SA
    Murch, SJ
    Cox, PA
    [J]. JOURNAL OF ETHNOPHARMACOLOGY, 2006, 106 (01) : 97 - 104
  • [4] Bergman Birgitta, 2008, P447
  • [5] Cyanobacterial blooms and the occurrence of the neurotoxin, beta-N-methylamino-L-alanine (BMAA), in South Florida aquatic food webs
    Brand, Larry E.
    Pablo, John
    Compton, Angela
    Hammerschlag, Neil
    Mash, Deborah C.
    [J]. HARMFUL ALGAE, 2010, 9 (06) : 620 - 635
  • [6] El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis
    Brooks, BR
    Miller, RG
    Swash, M
    Munsat, TL
    [J]. AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS, 2000, 1 (05): : 293 - 299
  • [7] Excitotoxic potential of the cyanotoxin β-methyl-amino-L-alanine (BMAA) in primary human neurons
    Chiu, Alexander S.
    Gehringer, Michelle M.
    Braidy, Nady
    Guillemin, Gilles J.
    Welch, Jeffrey H.
    Neilan, Brett A.
    [J]. TOXICON, 2012, 60 (06) : 1159 - 1165
  • [8] Does α-Amino-β-methylaminopropionic Acid (BMAA) Play a Role in Neurodegeneration?
    Chiu, Alexander S.
    Gehringer, Michelle M.
    Welch, Jeffrey H.
    Neilan, Brett A.
    [J]. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 2011, 8 (09): : 3728 - 3746
  • [9] Detection and quantification of β-methylamino-L-alanine in aquatic invertebrates
    Christensen, Stephanie J.
    Hemscheidt, Thomas K.
    Trapido-Rosenthal, Henry
    Laws, Edward A.
    Bidigare, Robert R.
    [J]. LIMNOLOGY AND OCEANOGRAPHY-METHODS, 2012, 10 : 891 - 898
  • [10] SYNTHESIS OF A FLUORESCENT DERIVATIZING REAGENT, 6-AMINOQUINOLYL-N-HYDROXYSUCCINIMIDYL CARBAMATE, AND ITS APPLICATION FOR THE ANALYSIS OF HYDROLYSATE AMINO-ACIDS VIA HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY
    COHEN, SA
    MICHAUD, DP
    [J]. ANALYTICAL BIOCHEMISTRY, 1993, 211 (02) : 279 - 287