海洋环境中神经毒素BMAA的溯源及其生态健康风险研究

According to the most recent studies, the neurotoxin BMAA, β-N-methylamino-L-alanine, has been universally detected in marine mollusk samples analyzed in previous works, and its suspected origin was from diatoms. The environmental BMAA toxin has been demonstrated as an important trigger for neurodegenerative disease including sporadic Alzheimer's disease. Recently the BMAA has been detected in the gastropod Neverita didyma collected from the Chinese coast. The neurotoxin BMAA will be critically analyzed in this proposal. Firstly, an international inter-laboratory test for BMAA in the gastropod Neverita didyma will be carried out in order to develop an effective method for BMAA analysis. Based on the accurate analysis method, samples of phytoplankton, zooplankton, mollusk, and fish, will be collected from the Jiaozhou Bay in four different seasons for one year, respectively. Taking into consideration the variation of BMAA in these samples and temporal-spatial variation of the density of phytoplankton species, the origin of BMAA and its possible bio-magnification pathway along food chains will be explored. The gastropod Neverita didyma will be targeted to disclose the source of BMAA detected in this typical mollusk animal. Eleven species of phytoplankton, zooplankton, mollusks, and fish will be experimentally exposed to different concentrations of BMAA, and the activity of antioxidant enzymes will be tested as a very sensitive biomarker for the damage caused by BMAA, in order to determine the maximal non-effect dose of BMAA toxin. The safe dose of marine environmental BMAA exposure will also be derived in this study. The anticipated goals of this proposal are very significant to the protection of seafood safety and human health.

最新研究发现，神经毒素BMAA（β-N-甲氨基-L-丙氨酸）在海水养殖贝类中普遍存在，推测其来源与硅藻有关。环境BMAA毒素可能是诱导散发的阿氏痴呆症的重要环境因子。本项目以BMAA为研究对象，以新发现的扁玉螺为典型染毒贝类，组织国内外实验室间的互校实验，建立液相色谱-串联质谱联用（LC-MS/MS）精准分析贝类BMAA的方法。选择胶州湾为重点调查海区，分别在一年四季定期采集浮游植物、浮游动物、贝类和鱼类等样品，检测不同生物样品中BMAA的含量，并结合浮游植物种群密度的季节变化规律，探讨BMAA分布的季节差异及其生物放大途径。以扁玉螺为重点研究对象，调查分析长山群岛、桑沟湾、舟山等海域底栖生物染毒的情况，重点探讨扁玉螺体内BMAA毒素的来源。选择浮游植物、浮游动物、贝类和鱼类等11种生物，分别与BMAA进行毒性暴露实验，以抗氧化酶活性作为灵敏的生物标志物，统计分析BMAA对海洋生物的最大无作用剂量，并推导该毒素的海洋环境质量基准。预期目标对于保障水产品安全和保护人体健康具有重要科学意义。

近年人们发现β-N-甲氨基-L-丙氨酸（BMAA）是诱发阿尔茨海默症、帕金森痴呆症等神经退行性疾病的重要环境因子。为此，本项目针对BMAA毒素的检测方法、生物毒性、食物链传递、环境来源等内容开展系统研究，以期揭示我国海洋环境中BMAA的来源及其对海洋生物、人体健康的风险。.项目组织法国和美国两家实验室参加了扁玉螺（Neverita didyma）样品中BMAA分析的互校实验，验证了项目所用BMAA分析方法的可靠性。项目首次报道了扁玉螺是BMAA的典型携带生物，最高含量可达42.37µg/g湿重，且我国舟山以北海区分布的软体动物普遍检出BMAA。从扁玉螺肠道分离培养的7种微生物，均未检出BMAA，但都含有BMAA的异构体DAB（2,4-二氨基丁酸）。2019年在胶州湾实施了4个季节的周年调查，发现BMAA沿浮游植物（生产者）-浮游动物（初级消费者）-软体动物和节肢动物（次级消费者）具有明显的生物放大现象，BMAA在浮游动物、双壳类软体动物、食肉性甲壳动物和腹足纲软体动物中的营养级放大因子分别为4.58、30.1、42.5和74.4；同时发现分离自我国沿海的海链藻（Thalassiosira spp.）、伪菱形藻（Pseudo-nitzschia spp.）、角毛藻（Chaetoceros spp.）等多种硅藻藻株含有BMAA。在室内选择球等鞭金藻（Isochrysis galbana）、太平洋亚历山大藻（Alexandrium pacificum）、卤虫（Artemia salina）、黑褐新糠虾（Neomysis awatschensis）、斑马鱼（Danio rerio）、海胆（Lytechinus pictus）等不同受试生物，开展了BMAA毒素的暴露实验，结果表明BMAA显著抑制球等鞭金藻的有丝分裂和生长，太平洋亚历山大藻的生长未见明显影响；黑褐新糠虾能够从水体中积累溶解态的BMAA，未见急性毒性作用；腹腔注射BMAA的染毒途径对斑马鱼的短期学习和记忆能力产生一定的负面影响；BMAA显著抑制海胆精子的受精能力和胚胎的早期发育并诱发畸形。.本研究首次揭示了我国胶州湾生态系统中BMAA的分布及其沿食物网的生物放大现象，指出硅藻是海洋环境中BMAA的重要来源，并为BMAA毒素海洋生物水质基准的推导奠定了基础，对于保护人类健康具有重要科学意义。