吴冬梅;张雁秋;程伟;陆军;郑元林;

• 1:中国矿业大学环境与测绘学院
• 2:江苏师范大学生命科学学院江苏省药用植物生物技术重点实验室

摘要(Abstract)：

在拟菱形藻引发的有毒赤潮中产生的记忆缺失性贝毒(amnesic shellfish poison,ASP)软骨藻酸,经贝类等海洋生物摄入进入食物链,在对海洋生物造成危害的同时,也对人类健康造成威胁。软骨藻酸中毒者临床上表现为呕吐、腹痛和头痛等症状,严重者出现神经系统功能紊乱,如昏迷、抽搐和记忆缺失。软骨藻酸结构上与兴奋性氨基酸谷氨酸相似,它可以通过直接活化KA(kainate)受体和AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)受体介导兴奋性神经毒。本文主要从线粒体功能紊乱、内质网应激和神经炎症等方面就软骨藻酸的神经毒性作用机制进行了综述。

关键词(KeyWords)： 软骨藻酸;兴奋性神经毒;认知损伤

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81271225;81171012;30950031);; 江苏省高校优势学科建设工程(PAPD);; 江苏省高校“青蓝工程”科技创新团队;; 江苏省高校自然科学基金(09KJB180009)

作者(Author): 吴冬梅;张雁秋;程伟;陆军;郑元林;

Email:

参考文献(References)：

• [1]Jeffery B,Barlow T,Moizer K,et al.Amnesic shellfish poison[J].Food and Chemical Toxicology,2004,42(4):545-557
• [2]Rhodes L,White D,Syhre M,et al.Pseudo-nitzschia species isolated from New Zealand coastal waters:Domo-ic acid production in vitro and links with shellfish toxicity[G]//Yasumoto T,Oshima Y,Fukuyo Y.Harmful andToxic Algal Blooms.Paris:Intergovermental Oceano-graphic Commission,UNESCO,1996:155-158
• [3]Cho E S,Kotaki Y,Park J G.The comparison between toxic Pseudo-nitzschia multiseries(Hasle)Hasle and non-toxic P.pungens(Grunow)Hasle isolated from Jinhae Bay,Korea[J].Algae,2001,16(3):275-285
• [4]Kawatsu K,Hamano Y,Noguchi T.Determination of do-moic acid in Japanese mussels by enzyme immunoassay[J].Journal of AOAC International,2000,83(6):1384-1386
• [5]Perl T M,B dard L,Kosatsky T,et al.An outbreak of toxic encephalopathy caused by eating mussels contami-nated with domoic acid[J].New England Journal of Medicine,1990,322(25):1775-1780
• [6]Lage S,Raimundo J,Brotas V,et al.Detection and sub-cellular distribution of the amnesic shellfish toxin,domoic acid,in the digestive gland of Octopus vulgaris during pe-riods of toxin absence[J].Marine Biology Research,2012,8(8):784-789
• [7]Scholin C A,Gulland F,Doucette G J,et al.Mortality of sea lions along the central California coast linked to a tox-ic diatom bloom[J].Nature,2000,403(6765):80-84
• [8]Brodie E C,Gulland F M D,Greig D J,et al.Domoic acid causes reproductive failure in California sea lions(Zalophus californianus)[J].Marine Mammal Science,2006,22(3):700-707
• [9]de la Riva G T,Johnson C K,Gulland F M D,et al.As-sociation of an unusual marine mammal mortality event with Pseudo-nitzschia sp.blooms along the southern Cal-ifornia coastline[J].Journal of Wildlife Diseases,2009,45(1):109-121
• [10]Lefebvre K A,Bargu S,Kieckhefer T,et al.From sand-dabs to blue whales:The pervasiveness of domoic acid[J].Toxicon,2002,40(7):971-977
• [11]Silvagni P A,Lowenstine L J,Spraker T,et al.Pathology of domoic acid toxicity in California sea lions(Zalophus californianus)[J].Veterinary Pathology,2005,42(2):184-191
• [12]Teitelbaum J S,Zatorre R J,Carpenter S,et al.Neurolog-ic sequelae of domoic acid intoxication due to the ingest-ion of contaminated mussels[J].New England Journal of Medicine,1990,322(25):1781-1787
• [13]Lefebvre K A,Robertson A.Domoic acid and human ex-posure risks:A review[J].Toxicon,2010,56(2):218-230
• [14]Costa L G,Giordano G,Faustman E M.Domoic acid as a developmental neurotoxin[J].NeuroToxicology,2010,31(5):409-423
• [15]中华人民共和国国家质量监督检验检疫总局.SN/T2663—2010中华人民共和国出入境检验检疫行业标准[S].北京:中国标准出版社,2010
• [16]Steinhuser C,Gallo V.News on glutamate receptors in glial cells[J].Trends in Neurosciences,1996,19(8):339-345
• [17]Hampson D R,Manalo J L.The activation of glutamate receptors by kainic acid and domoic acid[J].Natural Tox-ins,1998,6(3-4):153-158
• [18]Swanson G T.Targeting AMPA and kainate receptors in neurological disease:Therapies on the horizon?[J].Neu-ropsychopharmacology,2009,34(1):249-250
• [19]Pulido O.Domoic acid toxicologic pathology:A review[J].Marine Drugs,2008,6(2):180-219
• [20]Berman F W,LePage K T,Murray T F.Domoic acid neurotoxicity in cultured cerebellar granule neurons is con-trolled preferentially by the NMDA receptor Ca2+influx pathway[J].Brain Research,2002,924(1):20-29
• [21]Nijjar M,Nijjar S.Domoic acid-induced neurodegenera-tion resulting in memory loss is mediated by Ca2+over-load and inhibition of Ca2+calmodulin-stimulated adeny-late cyclase in rat brain(review)[J].International Journal of Molecular Medicine,2000,6(4):377-389
• [22]Nicotera P,Orrenius S.The role of calcium in apoptosis[J].Cell Calcium,1998,23(2-3):173-180
• [23]Peng T I,Jou M J.Oxidative stress caused by mitochon-drial calcium overload[J].Annals of the New York Acad-emy of Sciences,2010,1201(1):183-188
• [24]Schinder A F,Olson E C,Spitzer N C,et al.Mitochon-drial dysfunction is a primary event in glutamate neuro-toxicity[J].The Journal of Neuroscience,1996,16(19):6125-6133
• [25]Pedersen P.Mitochondrial events in the life and death of animal cells:A brief overview[J].Journal of Bioenergetics and Biomembranes,1999,31(4):291-304
• [26]D'Autr aux B,Toledano M B.ROS as signalling mole-cules:Mechanisms that generate specificity in ROS ho-meostasis[J].Nature Reviews Molecular Cell Biology,2007,8(10):813-824
• [27]Wu D M,Lu J,Zheng Y L,et al.Small interfering RNA-mediated knockdown of protein kinase C zeta attenuates domoic acid-induced cognitive deficits in mice[J].Toxico-logical Sciences,2012,128(1):209-222
• [28]Lu J,Wu D M,Zheng Y L,et al.Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-α-mediated mitochondrial bi-ogenesis signaling in mice[J].Free Radical Biology and Medicine,2012,52(3):646-659
• [29]Lindholm D,Wootz H,Korhonen L.ER stress and neu-rodegenerative diseases[J].Cell Death and Differentiation,2006,13(3):385-392
• [30]Kudo T,Kanemoto S,Hara H,et al.A molecular chaper-one inducer protects neurons from ER stress[J].Cell Death and Differentiation,2007,15(2):364-375
• [31]Sokka A L,Putkonen N,Mudo G,et al.Endoplasmic re-ticulum stress inhibition protects against excitotoxic neu-ronal injury in the rat brain[J].the Journal of Neuro-science,2007,27(4):901-908
• [32]Chandrasekaran A,Ponnambalam G,Kaur C.Domoic acid-induced neurotoxicity in the hippocampus of adult rats[J].Neurotoxicity Research,2004,6(2):105-117
• [33]Ryan J C,Cross C A,Van Dolah F M.Effects of COX inhibitors on neurodegeneration and survival in mice ex-posed to the marine neurotoxin domoic acid[J].Neuro-science Letters,2011,487(1):83-87
• [34]Goldstein T,Mazet J A K,Zabka T S,et al.Novel symptomatology and changing epidemiology of domoic acid toxicosis in California sea lions(Zalophus california-nus):An increasing risk to marine mammal health[J].Proceedings of the Royal Society B:Biological Sciences,2008,275(1632):267-276
• [35]Thomas K,Harvey J T,Goldstein T,et al.Movement,dive behavior,and survival of California sea lions(Zalo-phus californianus)posttreatment for domoic acid toxico-sis[J].Marine Mammal Science,2010,26(1):36-52
• [36]Sutherland R J,Hoesing J M,Whishaw I Q.Domoic acid,an environmental toxin,produces hippocampal damage and severe memory impairment[J].Neuroscience Letters,1990,120(2):221-223
• [37]Fuquay J M,Muha N,Pennington P L,et al.Domoic acid induced status epilepticus promotes aggressive be-havior in rats[J].Physiology&Behavior,2012,105(2):315-320
• [38]Baron A W,Rushton S P,Rens N,et al.Sex differences in effects of low level domoic acid exposure[J].Neuro-Toxicology,2013,34(1):1-8