β-N-Methylamino-l-alanine (BMAA), a neurotoxin naturally produced by cyanobacteria, diatoms and dinoflagellates, constitutes a serious environmental and health threat especially during acute blooms, which are becoming more frequent. This neurotoxin is implicated in several neurodegenerative diseases (ND) in humans through contaminated water or food consumption. Even low doses of neurotoxic compounds (NCs) can have lasting effects later in life. In this sense, early stages of development constitute a period of high sensitivity to environmental influence, particularly for the central nervous system. To understand the mechanisms underlying the delayed effects of NCs, newly hatched larvae of the mangrove rivulus fish, Kryptolebias marmoratus, were exposed to two sub-lethal doses of BMAA (20 μg/L and 15 mg/L) for 14 days. This fish naturally produces isogenic lineages due to its self-fertilizing reproduction, which is unique case among vertebrates. It thus provides genetic characteristics that allow scientists to study organisms’ true reaction norm, minimizing genetic variability and focusing exclusively on the effects of the environment. Effect assessment was performed at different levels of biological organization to detect inconspicuous effects of BMAA, since this molecule displays long retention in organisms. BMAA effects on life history traits as well as behavioral traits such as boldness and aggressiveness were assessed more than 100 days after exposure. In addition, the relative expression of 7 potential BMAA target genes was studied, given their involvement in neurotransmission or their association with individual variation in boldness and aggressiveness. Selected genes code for reticulon 4 (RTN4), glutamate vesicular transporter 1 (Slc17a7), glutamine synthetase a (Glula), dopamine receptor D4 (DRD4), monoamine oxidase A (MAOA), calmodulin (CaM) and epedymine (Epd). Despite observing no effects of BMAA on growth, reproduction and behavioral traits, BMAA induced a significant increase of the expression of CaM and MAOA genes at 20 μg/L BMAA compared to the control group. A significant decrease of expression was observed between this lowest BMAA dose and 15 mg/L for DRD4, MAOA and CaM genes. Our results suggest disruption of glutamate turnover, intracellular dopamine depletion and activation of astrocyte protective mechanisms, indicating that BMAA might be excitotoxic. Our study revealed that BMAA can have long-lasting effects on the brain that are suspected to affect phenotypic traits with aging. Furthermore, it highlights the importance of studying delayed effects in ecotoxicological studies.

β- N-甲基氨基-1-丙氨酸（BMAA）是由蓝细菌，硅藻和鞭毛藻自然产生的一种神经毒素，对环境和健康构成了严重威胁，尤其是在急性开花期间，这种危害日益严重。通过污染的水或食物的摄入，这种神经毒素与人类的几种神经退行性疾病（ND）有关。即使是低剂量的神经毒性化合物（NCs）也可能在以后的生活中产生持久影响。从这个意义上讲，发展的早期阶段构成了对环境影响高度敏感的时期，尤其是对中枢神经系统。要了解引起NCs延迟效应的机制，即红树林小溪鱼Kryptolebias marmoratus刚孵出的幼虫，暴露于两种亚致死剂量的BMAA（20μg/ L和15 mg / L）中，持续14天。这种鱼由于自身受精繁殖而自然产生同基因谱系，这在脊椎动物中是独特的情况。因此，它提供了遗传特征，使科学家能够研究生物体的真实反应规范，最大程度地降低遗传变异性，并专注于环境的影响。在该生物组织的不同水平上进行了效果评估，以检测BMAA的不起眼的效果，因为该分子在生物体中显示了长时间的保留。在接触后超过100天，评估了BMAA对生活史特征以及诸如胆大和攻击性等行为特征的影响。此外，还研究了7个潜在BMAA靶基因的相对表达，考虑到他们参与神经传递或与胆大和攻击性的个体差异有关。选定的基因编码为网状蛋白4（RTN4），谷氨酸水泡转运蛋白1（Slc17a7），谷氨酰胺合成酶a（Glula），多巴胺受体D4（DRD4），单胺氧化酶A（MAOA），钙调蛋白（CaM）和乙二胺（Epd）。尽管没有观察到BMAA对生长，繁殖和行为特征的影响，但是与对照组相比，在20μg/ L BMAA下BMAA诱导了CaM和MAOA基因表达的显着增加。在最低的BMAA剂量与DRD4，MAOA和CaM基因的15 mg / L之间观察到表达显着降低。我们的结果表明，谷氨酸转换，细胞内多巴胺耗竭和星形胶质细胞保护机制的激活受到破坏，表明BMAA可能具有兴奋性毒性。我们的研究表明BMAA可能对大脑具有长效作用，这种作用被怀疑会随着年龄的增长而影响表型特征。此外，它强调了在生态毒理学研究中研究延迟效应的重要性。