Tiedeken Jessica A, Ramsdell John S, Ramsdell Ann F
Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, NOAA, National Ocean Service, 219 Fort Johnson Rd., Charleston, SC 29412, USA.
Neurotoxicol Teratol. 2005 Sep-Oct;27(5):711-7. doi: 10.1016/j.ntt.2005.06.013. Epub 2005 Aug 2.
Domoic acid (DA) is a rigid analog of the excitatory amino acid glutamate. It is produced by the diatom genus Pseudo-nitzschia and is a potent neurotoxin in both adult and developing animals. We have used zebrafish (Danio rerio) as a model to investigate and characterize the developmental toxicity of DA. Domoic acid was administered by microinjection to fertilized eggs at the 128- to 512-cell stages in concentrations ranging from 0.12 to 17 mg/kg (DA/egg weight). DA reduced hatching success by 40% at 0.4 mg/kg and by more than 50% at doses of 1.2 mg/kg and higher. Fifty percent of embryos treated with 1.2 mg/kg DA showed marked tonic-clonic type convulsions at 2 days post fertilization. Four days post fertilization (dpf), all embryos treated with 4.0 mg/kg DA and higher showed a complete absence of touch response reflexes. Commencing 5 dpf, rapid and constant pectoral fin movements were observed, a response which may be related to the hallmark effect in rodents of stereotypic scratching. These data indicate that zebrafish show symptoms of developmental DA toxicity as well as a similar sensitivity comparable to the effects of DA characterized in laboratory rodents.
软骨藻酸(DA)是兴奋性氨基酸谷氨酸的刚性类似物。它由拟菱形藻属硅藻产生,对成年动物和发育中的动物都是一种强效神经毒素。我们以斑马鱼(Danio rerio)为模型来研究和表征DA的发育毒性。在128至512细胞阶段,通过显微注射将软骨藻酸以0.12至17毫克/千克(DA/卵重)的浓度施用于受精卵。软骨藻酸在0.4毫克/千克时使孵化成功率降低40%,在1.2毫克/千克及更高剂量时降低超过50%。用1.2毫克/千克软骨藻酸处理的胚胎中有50%在受精后2天出现明显的强直阵挛型惊厥。受精后4天(dpf),用4.0毫克/千克及更高剂量软骨藻酸处理的所有胚胎均完全没有触觉反应反射。从5 dpf开始,观察到快速且持续的胸鳍运动,这种反应可能与啮齿动物中刻板抓挠的标志性效应有关。这些数据表明,斑马鱼表现出发育性DA毒性症状,并且具有与实验室啮齿动物中所表征的DA效应相当的敏感性。