Laboratório de Neuroquímica e Psicofarmacologia, Escola de Ciências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Laboratório de Biologia Genômica e Molecular, Escola de Ciências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neurotoxicol Teratol. 2018 Nov-Dec;70:60-66. doi: 10.1016/j.ntt.2018.10.004. Epub 2018 Oct 24.
Prenatal alcohol exposure causes alterations to the brain and can lead to numerous cognitive and behavioral outcomes. Long-lasting effects of early ethanol exposure have been registered in glutamatergic and dopaminergic systems. The purinergic system has been registered as an additional target of ethanol exposure. The objective of this research was to evaluate if the ecto‑5'‑nucleotidase and adenosine deaminase activities and gene expression of adult zebrafish exposed to 1% ethanol during early development could be part of the long-lasting targets of ethanol. Zebrafish embryos were exposed to 1% ethanol in two distinct developmental phases: gastrula/segmentation (5-24 h post-fertilization) or pharyngula (24-48 h post-fertilization). At the end of three months, after checking for morphological outcomes, the evaluation of enzymatic activity and gene expression was performed. Exposure to ethanol did not promote gross morphological defects; however, a significant decrease in the body length was observed (17% in the gastrula and 22% in the pharyngula stage, p < 0.0001). Ethanol exposure during the gastrula/segmentation stage promoted an increase in ecto‑5'‑nucleotidase activity (39.5%) when compared to the control/saline group (p < 0.0001). The ecto‑5'‑nucleotidase gene expression and the deamination of adenosine exerted by ecto and cytosolic adenosine deaminase were not affected by exposure to ethanol in both developmental stages. HPLC experiments did not identify differences in adenosine concentration on the whole encephala of adult animals exposed to ethanol during the gastrula stage or on control animals (p > 0.05). Although the mechanism underlying these findings requires further investigation, these results indicate that ethanol exposure during restricted periods of brain development can have long-term consequences on ecto‑5'‑nucleotidase activity, which could have an impact on subtle sequels of ethanol early exposure.
产前酒精暴露会导致大脑发生变化，并可能导致多种认知和行为结果。早期乙醇暴露的持久影响已在谷氨酸能和多巴胺能系统中得到证实。嘌呤能系统已被证实是乙醇暴露的另一个靶标。本研究的目的是评估在早期发育过程中暴露于 1%乙醇的成年斑马鱼的外核苷酸酶和腺苷脱氨酶活性和基因表达是否可能成为乙醇的长期靶标之一。斑马鱼胚胎在两个不同的发育阶段暴露于 1%乙醇：原肠胚/体节（受精后 5-24 小时）或咽胚（受精后 24-48 小时）。在三个月结束时，在检查形态学结果后，进行了酶活性和基因表达的评估。乙醇暴露并未导致明显的形态学缺陷；然而，观察到体长显著缩短（原肠胚阶段为 17%，咽胚阶段为 22%，p<0.0001）。与对照组/盐水组相比，原肠胚/体节阶段暴露于乙醇可使外核苷酸酶活性增加 39.5%（p<0.0001）。在两个发育阶段，外核苷酸酶基因表达和外切和胞质腺苷脱氨酶对腺苷的脱氨作用均不受乙醇暴露的影响。HPLC 实验未发现暴露于乙醇的成年动物的整个脑或对照动物的腺苷浓度存在差异（p>0.05）。尽管这些发现的机制需要进一步研究，但这些结果表明，在大脑发育的特定时期暴露于乙醇可能对外核苷酸酶活性产生长期影响，这可能对早期乙醇暴露的微妙后果产生影响。
