武汉官桥湖蓝藻毒素BMAA的生物累积与健康风险评估
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摘要
鉴于蓝藻"水华"能产生新型神经毒素-β-N-甲氨基-L-丙氨酸(β-N-methylamino-L-alanine,BMAA),并通过生物富集作用在水生态系统的各营养级进行传递;选取武汉东湖子湖—官桥湖,采用HPLC-MS/MS分析方法,在蓝藻水华暴发期间,测定湖水、蓝藻及鱼体内游离态和蛋白结合态BMAA毒素的含量。结果表明,在水体中未检测到溶解态BMAA(在检测限0.05μg/L以下),但在微囊藻细胞及鱼体内(干重)均能检测到,含量均值分别为(0.040±0.002)μg/g和(0.32±0.317)μg/g,说明官桥湖在暴发水华后,蓝藻产生了BMAA毒素且被鱼类吸收和放大;不同鱼体(干重)累积BMAA的程度不同,总BMAA含量(干重)分别为鳑鲏(0.243±0.205)μg/g,鲫(0.126±0.040)μg/g,鲤(0.613±0.120)μg/g,鲢(0.028±0.018)μg/g,鳙(0.039±0.021)μg/g,鳊(0.879±0.243)μg/g;鲤和鳊的富集浓度较高,且与其它几种鱼有显著性差异(P<0.05)。按照WHO生活饮用水安全标准的建议进行推算,官桥湖鱼肉EDI值(估算的每天摄入量)为1.015μg/(kg·d),显著低于估算出的TDI值(日容许摄入量)0.5mg/(kg·d),基本不会对人造成急性中毒,但由于BMAA毒素为慢性毒素,不能忽视经常食用鱼肉后的累积风险。建议有关部门将东湖水产品的BMAA毒素纳入长期监测。
N-methylamino-L-alanine(BMAA)is a newly identified neurotoxin produced during cyanobacterial blooms,and bioaccumulation of BMAA can lead to food chain amplification.Guanqiao Lake,an area of Donghu Lake in Wuhan,is a typical eutrophic urban lake with frequent algal blooms.In this study,we investigated the distribution of BMAA in Guanqiao Lake during a cyanobacterial bloom in July,2017.Free BMAA and protein-bound BMAA in the water column and BMAA extracted from cyanobacteria and fish samples were analyzed by HPLC-MS/MS.The study provides scientific data to support environmental management of urban lakes and early warning when human health is threatened by cyanotoxins.FreeBMAA in the water column was below the detection limit(0.05μg/L),but BMAA was detected in microcystis(0.04±0.002μg/g,dw)and fish(0.32±0.317μg/g,dw).Furthermore,determination of BMAA in fish species occupying different trophic levels indicates that BMAA can be bioamplified as it moves up the food chain.The BMAA concentration in Rhodeus sinensis,Carassius auratus,Cyprinus carpio,Hypophthalmichthys molitrix,Aristichthys nobilis and Parabramis pekinensis were,respectively,(0.243±0.205)μg/g,(126±0.04)μg/g,(0.613±0.120)μg/g,(0.028±0.018)μg/g,(0.039±0.021)μg/g and(0.879±0.243)μg/g.The BMAA concentrations in Cyprinus carpio and Parabramis pekinensis were significantly higher than in the other species(P<0.05).According to WHO drinking water guidelines,the EDI(Estimated Daily Intake)values of BMAA from fish was 1.015μg/(kg·d),considerably lower than the estimated TDI(Tolerable Daily Intake)value of 0.5 mg/(kg·d).This indicates that the health risk of consuming fish from Guanqiao Lake is relatively low and not likely cause acute toxicity in humans.However,due to the potential for a chronic response,the risk of BMAA accumulation should not be ignored.Therefore,we recommend long-term monitoring of BMAA in fish from Donghu Lake by the relevant regulatory agencies.
N-methylamino-L-alanine(BMAA)is a newly identified neurotoxin produced during cyanobacterial blooms,and bioaccumulation of BMAA can lead to food chain amplification.Guanqiao Lake,an area of Donghu Lake in Wuhan,is a typical eutrophic urban lake with frequent algal blooms.In this study,we investigated the distribution of BMAA in Guanqiao Lake during a cyanobacterial bloom in July,2017.Free BMAA and protein-bound BMAA in the water column and BMAA extracted from cyanobacteria and fish samples were analyzed by HPLC-MS/MS.The study provides scientific data to support environmental management of urban lakes and early warning when human health is threatened by cyanotoxins.FreeBMAA in the water column was below the detection limit(0.05μg/L),but BMAA was detected in microcystis(0.04±0.002μg/g,dw)and fish(0.32±0.317μg/g,dw).Furthermore,determination of BMAA in fish species occupying different trophic levels indicates that BMAA can be bioamplified as it moves up the food chain.The BMAA concentration in Rhodeus sinensis,Carassius auratus,Cyprinus carpio,Hypophthalmichthys molitrix,Aristichthys nobilis and Parabramis pekinensis were,respectively,(0.243±0.205)μg/g,(126±0.04)μg/g,(0.613±0.120)μg/g,(0.028±0.018)μg/g,(0.039±0.021)μg/g and(0.879±0.243)μg/g.The BMAA concentrations in Cyprinus carpio and Parabramis pekinensis were significantly higher than in the other species(P<0.05).According to WHO drinking water guidelines,the EDI(Estimated Daily Intake)values of BMAA from fish was 1.015μg/(kg·d),considerably lower than the estimated TDI(Tolerable Daily Intake)value of 0.5 mg/(kg·d).This indicates that the health risk of consuming fish from Guanqiao Lake is relatively low and not likely cause acute toxicity in humans.However,due to the potential for a chronic response,the risk of BMAA accumulation should not be ignored.Therefore,we recommend long-term monitoring of BMAA in fish from Donghu Lake by the relevant regulatory agencies.
引文
陈晓国,肖邦定,徐小清,等,2004.不同波段紫外光对微囊藻毒素光降解的影响[J].中国环境科学,24(1):1-5.
甘义群,郭永龙,2004.武汉东湖富营养化现状分析及治理对策[J].长江流域资源与环境,13(3):277-281.
贾军梅,罗维,吕永龙,等,2014.微囊藻毒素在太湖白鲢体内的累积规律及其影响因素[J].生态毒理学报,9(2):382-390.
罗凯,2009.蓝藻水华治理方法比较及武汉官桥湖治理浅析[J].科协论坛,(10):124.
施丽梅,蔡元锋,杨华林,等,2009.太湖梅梁湾水华微囊藻基因型组成和产毒微囊藻丰度的变化[J].湖泊科学,21(6):801-805.
陶新园,沈冬,赖树锦,等,2016.武汉市东湖不同区域水体水质和富营养化分析[J].湖北农业科学,55(10):2504-2506.
温周瑞,王丛丹,李文华,等,2013.武汉城市湖泊水质及水体富营养化现状评价[J].水生态学杂志,34(5):62-64.
余博识,吴忠兴,朱梦灵,等,2008.水果湖湾蓝藻水华的形成及其对东湖影响的评价[J].水生生物学报,32(2):286-289.
张维昊,2001.滇池微囊藻毒素的环境化学行为研究[D].武汉:中国科学院水生生物研究所.
Al-Sammak M,Hoagland K,Cassada D,et al,2014.Co-occurrence of the cyanotoxins BMAA,DABA and Anatoxin-a in Nebraska reservoirs,fish,and aquatic plants[J].Toxins,6(2):488-508.
Andersson M,Ersson L,Brandt I,et al,2017.Potential transfer of neurotoxic amino acidβ-N-methylamino-alanine(BMAA)from mother to infant during breastfeeding:Predictions from human cell lines[J].Toxicology and Applied Pharmacology,320:40-50.
Andersson M,Karlsson O,Brand I,2018.The environmental neurotoxinβ-N-methylamino-L-alanine(L-BMAA)is deposited into birds′eggs[J].Ecotoxicology and Environmental Safety,147:720-724.
Banack S A,Cox P A,2003a.Biomagnification of cycad neurotoxins in flying foxes[J].Neurology,61:387-389.
Banack S A,Cox P A,2003b.Distribution of the neurotoxic nonprotein amino acid BMAA in Cycas micronesica[J].Bot J Linn Soc,143:165-168.
Banack S A,Murch S J,Cox P A,2006.Neurotoxic fiying foxes as dietary items for the Chamorro people,Marianas Islands[J].J Ethnopharmacol,106:97-104.
Bittencourt Oliveira M C,2003.Detection of potential microcystin producing cyanobacteria in Brazilian reservoirs with a mcyB molecularmarker[J].Harmful Algae,2(1):51-60.
Brand L E,Pablo J,Compton A,et al,2010.Cyanobacterial blooms and the occurrence of the neurotoxin,beta-N-methylamino-L-alanine(BMAA),in South Florida aquatic food webs[J].Harmful Algae,9:620-635.
Christensen S J,Hemscheidt T K,Trapido-Rosenthal H,et al,2012.Detection and quantification ofβ-N-methylamino-L-alanine in aquatic invertebrates[J].Limnol Oceanogr-Meth,10:891-898.
Codd G A,Morrison L F,Metcalf J S,2005.Cyanobacterial toxins:risk management for health protection[J].Toxicology and Applied Pharmacology,203:264-272.
Cox P A,Sacks O W,2002.Cycad neurotoxins,consumption of flying foxes and ALS-PDC disease in Guam[J].Neurology,58:956-959.
Cox P A,Banack S A,Murch S J,2003.Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam[J].Proc Natl Acad Sci USA,100:13380-13383.
Cox P A,Banack S A,Murch S J,et al,2005.Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine,a neurotoxic amino acid[J].Proc Natl Acad Sci USA,102:5074-5078.
Esterhuizen M,Downing T G,2011.Solid phase extraction ofβ-N-methylamino-L-alanine(BMAA)from South African water supplies[J].Water SA,37:523-528.
Engskog M K R,Ersson L,Haglf J,et al,2017.β-N-methylamino-L-alanine(BMAA)perturbs alanine,aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling[J].Amino Acids,49:905-919.
Falconer I R,Humpage A R,2005.Health Risk Assessment of Cyanobacterial(Blue-green Algal)Toxins in Drinking Water[J].Inter J Env Res Pub Heal,2:43-50.
Hammerschlag N,Davis D V,Mondo K,et al,2016.Cyanobacterial Neurotoxin BMAA and Mercury in Sharks[J].Toxins,8:238-251.
Jiang L,Kiselova N,Rosén J,et al,2014.Quantification of neurotoxin BMAA(β-N-methylamino-L-alanine)in seafood from Swedish markets[J].Scientific Reports,4:6931-6937.
Jiao Y Y,Chen Q K,Chen X,et al,2014.Occurrence and transfer of a cyanobacterial neurotoxinβ-methylaminoL-alanin-e within the aquatic food webs of Gonghu Bay(Lake Taihu,China)to evaluate the potential human health risk[J].Science of the Total Environment,468/469:457-463.
Jonasson S,Eriksson J,Berntzon L,et al,2010.Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure[J].Proc Natl Acad Sci USA,107:9252-9257.
Kardinaal W E A,Janse I,Kamst-van Agterveld M et al,2007.Microcystis genotype succession in relation to microcystin concentrations in freshwater lakes[J].Aquatic Microbiology Ecology,48:1-12.
Kerrin E S,White R L,Quilliam M A,2017.Quantitative determination of the neurotoxinβ-N-methylamino-L-alanine(BMAA)by apillary electrophoresis-tandem mass spectrometry[J].Analytical and Bioanalytical Chemistry,409(6):1481-1491.
Lachapelle A R,Solliec M,Bouchard M F,et al,2017.Detection of Cyanotoxins in Algae Dietary Supplements[J].Toxins,9:76-92.
Li A,Tian Z,Li J,et al,2010.Detection of the neurotoxin BMAA within cyanobacteria isolated from freshwater in China[J].Toxicon,55:947-953.
Lobner D,Piana P M T,Salous A K,et al,2007.β-N-methylamino-l-alanine enhances neurotoxicity through multiple mechanisms[J].Neurobiology of disease,25:360-366.
Mcintyre J K,Beauchamp D A,2007.Age and trophic position dominate bioaccumulation of mercury and organochlorines in the food web of Lake Washington[J].Science of the Total Environment,372(2/3):571-584.
Metcalf J S,Banack S A,Lindssay J,et al,2008.Co-occurrence ofβ-N-methylamino-L-alanine,a neurotoxic amino acid with other cyanobacterial toxins in British waterbodies,1990-2004[J].Environ Microbiol,10:702-708.
Mondo K,Hammerschlag N,Basile M,et al,2010.Cyanobacterial Neurotoxinβ-N-Methylamino-L-alanine(BMAA)in Shark Fins[J].Marine Drugs,10:509-520.
Murch S J,Cox P A,Banack S A,2004a.A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam[J].Proc Natl Acad Sci USA,101:12228-12231.
Murch S J,Cox P A,Banack S A,et al,2004b.Occurrence ofβ-methylamino-l-alanine(BMAA)in ALS/PDC patients from Guam[J].Acta Neurologica Scandinavica,110:267-269.
Perry T L,Bergeron C,Biro A J,et al,1989.Beta-N-methylamino-L-alanine.Chronic oral administration is not neurotoxic to mice[J].Journal of the Neurological Sciences,94:173-180.
Polsky F I,Nunn P B,Bell E A,1972.Distribution and toxicity of alpha-amino-beta-methylaminoproprionic acid[J].Fed Proc,31:1473-1472.
Purdie E L,Samsudin S,Eddy F B,et al,2009.Effects of the cyanobacterial neurotoxinβ-N-methylamino-L-alanine on the early-life stage development of zebrafish Danio rerio[J].Aquatic Toxicology,95:279-284.
Rakonczay Z,Matsuoka Y,Giacobini E,1991.Effects of L-beta-N-methylamino-L-alanine(L-BMAA)on the cortical cholinergic and glutamatergic systems of the rat[J].Journal of Neuroscience Research,29:121-126.
Réveillon D,Séchet V,Hess P,et al,2016.Systematic detection of BMAA(b-N-methylamino-L-alanine)and DAB(2,4-diaminobutyric acid)in mollusks collected in shellfish production areas along the French coasts[J].Toxicon,110:35-46.
Snyder L R,Cruz-Aguado R,Sadilek M,et al,2009.Parkinson-dementia complex and development of a new stable isotope dilution assay for BMAA detection in tissue[J].Toxicology and Applied Pharmacology,240:180-188.
Spencer P S,Hunn P B,Hugon J,et al,1987a.Guam amyotrophic lateral sclerosis-Parkinsonism-dementia linked to a plant excitant neurotoxin[J].Science,237:517-522.
Spencer P S,Hugon J,Ludolph A,et al,1987b.Discovery and partial characterization of primate motor-system toxins[J].Ciba Foundation Symposium,126:221-238.
Staton P C,Bristow D R,1997.The dietary excitotoxinsβ-N-methylamino-L-alanine andβ-N-oxalylamino-L-alanine induce necrotic and apoptotic-like death of rat cerebellar granule cells[J].Journal of Neurochemistry,69:1508-1518.
Tan V X,Mazzocco C,Varney B,et al,2018.Detection of the Cyanotoxins L-BMAA Uptake and Accumulation in Primary Neurons and Astrocytes[J].Neurotoxicity Research,33:55-61.
WORLD HEALTH ORGANIZATION,1998.Cyanobacterial toxins:microcystin-LR:Guidelines for drinking-water quality[E].Geneva:WHO:95-110.
甘义群,郭永龙,2004.武汉东湖富营养化现状分析及治理对策[J].长江流域资源与环境,13(3):277-281.
贾军梅,罗维,吕永龙,等,2014.微囊藻毒素在太湖白鲢体内的累积规律及其影响因素[J].生态毒理学报,9(2):382-390.
罗凯,2009.蓝藻水华治理方法比较及武汉官桥湖治理浅析[J].科协论坛,(10):124.
施丽梅,蔡元锋,杨华林,等,2009.太湖梅梁湾水华微囊藻基因型组成和产毒微囊藻丰度的变化[J].湖泊科学,21(6):801-805.
陶新园,沈冬,赖树锦,等,2016.武汉市东湖不同区域水体水质和富营养化分析[J].湖北农业科学,55(10):2504-2506.
温周瑞,王丛丹,李文华,等,2013.武汉城市湖泊水质及水体富营养化现状评价[J].水生态学杂志,34(5):62-64.
余博识,吴忠兴,朱梦灵,等,2008.水果湖湾蓝藻水华的形成及其对东湖影响的评价[J].水生生物学报,32(2):286-289.
张维昊,2001.滇池微囊藻毒素的环境化学行为研究[D].武汉:中国科学院水生生物研究所.
Al-Sammak M,Hoagland K,Cassada D,et al,2014.Co-occurrence of the cyanotoxins BMAA,DABA and Anatoxin-a in Nebraska reservoirs,fish,and aquatic plants[J].Toxins,6(2):488-508.
Andersson M,Ersson L,Brandt I,et al,2017.Potential transfer of neurotoxic amino acidβ-N-methylamino-alanine(BMAA)from mother to infant during breastfeeding:Predictions from human cell lines[J].Toxicology and Applied Pharmacology,320:40-50.
Andersson M,Karlsson O,Brand I,2018.The environmental neurotoxinβ-N-methylamino-L-alanine(L-BMAA)is deposited into birds′eggs[J].Ecotoxicology and Environmental Safety,147:720-724.
Banack S A,Cox P A,2003a.Biomagnification of cycad neurotoxins in flying foxes[J].Neurology,61:387-389.
Banack S A,Cox P A,2003b.Distribution of the neurotoxic nonprotein amino acid BMAA in Cycas micronesica[J].Bot J Linn Soc,143:165-168.
Banack S A,Murch S J,Cox P A,2006.Neurotoxic fiying foxes as dietary items for the Chamorro people,Marianas Islands[J].J Ethnopharmacol,106:97-104.
Bittencourt Oliveira M C,2003.Detection of potential microcystin producing cyanobacteria in Brazilian reservoirs with a mcyB molecularmarker[J].Harmful Algae,2(1):51-60.
Brand L E,Pablo J,Compton A,et al,2010.Cyanobacterial blooms and the occurrence of the neurotoxin,beta-N-methylamino-L-alanine(BMAA),in South Florida aquatic food webs[J].Harmful Algae,9:620-635.
Christensen S J,Hemscheidt T K,Trapido-Rosenthal H,et al,2012.Detection and quantification ofβ-N-methylamino-L-alanine in aquatic invertebrates[J].Limnol Oceanogr-Meth,10:891-898.
Codd G A,Morrison L F,Metcalf J S,2005.Cyanobacterial toxins:risk management for health protection[J].Toxicology and Applied Pharmacology,203:264-272.
Cox P A,Sacks O W,2002.Cycad neurotoxins,consumption of flying foxes and ALS-PDC disease in Guam[J].Neurology,58:956-959.
Cox P A,Banack S A,Murch S J,2003.Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam[J].Proc Natl Acad Sci USA,100:13380-13383.
Cox P A,Banack S A,Murch S J,et al,2005.Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine,a neurotoxic amino acid[J].Proc Natl Acad Sci USA,102:5074-5078.
Esterhuizen M,Downing T G,2011.Solid phase extraction ofβ-N-methylamino-L-alanine(BMAA)from South African water supplies[J].Water SA,37:523-528.
Engskog M K R,Ersson L,Haglf J,et al,2017.β-N-methylamino-L-alanine(BMAA)perturbs alanine,aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling[J].Amino Acids,49:905-919.
Falconer I R,Humpage A R,2005.Health Risk Assessment of Cyanobacterial(Blue-green Algal)Toxins in Drinking Water[J].Inter J Env Res Pub Heal,2:43-50.
Hammerschlag N,Davis D V,Mondo K,et al,2016.Cyanobacterial Neurotoxin BMAA and Mercury in Sharks[J].Toxins,8:238-251.
Jiang L,Kiselova N,Rosén J,et al,2014.Quantification of neurotoxin BMAA(β-N-methylamino-L-alanine)in seafood from Swedish markets[J].Scientific Reports,4:6931-6937.
Jiao Y Y,Chen Q K,Chen X,et al,2014.Occurrence and transfer of a cyanobacterial neurotoxinβ-methylaminoL-alanin-e within the aquatic food webs of Gonghu Bay(Lake Taihu,China)to evaluate the potential human health risk[J].Science of the Total Environment,468/469:457-463.
Jonasson S,Eriksson J,Berntzon L,et al,2010.Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure[J].Proc Natl Acad Sci USA,107:9252-9257.
Kardinaal W E A,Janse I,Kamst-van Agterveld M et al,2007.Microcystis genotype succession in relation to microcystin concentrations in freshwater lakes[J].Aquatic Microbiology Ecology,48:1-12.
Kerrin E S,White R L,Quilliam M A,2017.Quantitative determination of the neurotoxinβ-N-methylamino-L-alanine(BMAA)by apillary electrophoresis-tandem mass spectrometry[J].Analytical and Bioanalytical Chemistry,409(6):1481-1491.
Lachapelle A R,Solliec M,Bouchard M F,et al,2017.Detection of Cyanotoxins in Algae Dietary Supplements[J].Toxins,9:76-92.
Li A,Tian Z,Li J,et al,2010.Detection of the neurotoxin BMAA within cyanobacteria isolated from freshwater in China[J].Toxicon,55:947-953.
Lobner D,Piana P M T,Salous A K,et al,2007.β-N-methylamino-l-alanine enhances neurotoxicity through multiple mechanisms[J].Neurobiology of disease,25:360-366.
Mcintyre J K,Beauchamp D A,2007.Age and trophic position dominate bioaccumulation of mercury and organochlorines in the food web of Lake Washington[J].Science of the Total Environment,372(2/3):571-584.
Metcalf J S,Banack S A,Lindssay J,et al,2008.Co-occurrence ofβ-N-methylamino-L-alanine,a neurotoxic amino acid with other cyanobacterial toxins in British waterbodies,1990-2004[J].Environ Microbiol,10:702-708.
Mondo K,Hammerschlag N,Basile M,et al,2010.Cyanobacterial Neurotoxinβ-N-Methylamino-L-alanine(BMAA)in Shark Fins[J].Marine Drugs,10:509-520.
Murch S J,Cox P A,Banack S A,2004a.A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam[J].Proc Natl Acad Sci USA,101:12228-12231.
Murch S J,Cox P A,Banack S A,et al,2004b.Occurrence ofβ-methylamino-l-alanine(BMAA)in ALS/PDC patients from Guam[J].Acta Neurologica Scandinavica,110:267-269.
Perry T L,Bergeron C,Biro A J,et al,1989.Beta-N-methylamino-L-alanine.Chronic oral administration is not neurotoxic to mice[J].Journal of the Neurological Sciences,94:173-180.
Polsky F I,Nunn P B,Bell E A,1972.Distribution and toxicity of alpha-amino-beta-methylaminoproprionic acid[J].Fed Proc,31:1473-1472.
Purdie E L,Samsudin S,Eddy F B,et al,2009.Effects of the cyanobacterial neurotoxinβ-N-methylamino-L-alanine on the early-life stage development of zebrafish Danio rerio[J].Aquatic Toxicology,95:279-284.
Rakonczay Z,Matsuoka Y,Giacobini E,1991.Effects of L-beta-N-methylamino-L-alanine(L-BMAA)on the cortical cholinergic and glutamatergic systems of the rat[J].Journal of Neuroscience Research,29:121-126.
Réveillon D,Séchet V,Hess P,et al,2016.Systematic detection of BMAA(b-N-methylamino-L-alanine)and DAB(2,4-diaminobutyric acid)in mollusks collected in shellfish production areas along the French coasts[J].Toxicon,110:35-46.
Snyder L R,Cruz-Aguado R,Sadilek M,et al,2009.Parkinson-dementia complex and development of a new stable isotope dilution assay for BMAA detection in tissue[J].Toxicology and Applied Pharmacology,240:180-188.
Spencer P S,Hunn P B,Hugon J,et al,1987a.Guam amyotrophic lateral sclerosis-Parkinsonism-dementia linked to a plant excitant neurotoxin[J].Science,237:517-522.
Spencer P S,Hugon J,Ludolph A,et al,1987b.Discovery and partial characterization of primate motor-system toxins[J].Ciba Foundation Symposium,126:221-238.
Staton P C,Bristow D R,1997.The dietary excitotoxinsβ-N-methylamino-L-alanine andβ-N-oxalylamino-L-alanine induce necrotic and apoptotic-like death of rat cerebellar granule cells[J].Journal of Neurochemistry,69:1508-1518.
Tan V X,Mazzocco C,Varney B,et al,2018.Detection of the Cyanotoxins L-BMAA Uptake and Accumulation in Primary Neurons and Astrocytes[J].Neurotoxicity Research,33:55-61.
WORLD HEALTH ORGANIZATION,1998.Cyanobacterial toxins:microcystin-LR:Guidelines for drinking-water quality[E].Geneva:WHO:95-110.
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