Contribuição do modelo animal zebrafish (Danio Rerio) nos estudos das consequências comportamentais da exposição precoce ao álcool : revisão sistemática

Abstract

Introduction: The Fetal Alcohol Spectrum Disorders (FASD) is a public health problem, with great morbidity in thousands of children, worldwide. Despite its frequency, behavioral changes related to exposure to alcohol during the embryonic period are still thought of as a diagnosis of exclusion and many children of this diagnostic spectrum mistaken with other neurobehavioral pathologies. The zebrafish has become a suitable animal model to investigate the effects of early exposure to ethanol, since it is easy to manipulate during the early development and ability to reproduce important features of FASD, including behavioral effects. Objective: To systematically review existing behavioral studies that address the impact of early alcohol exposure using zebrafish as an experimental FASD model. Methods: a systematic review was conducted in the databases MEDLINE, EMBASE, PUBMED, Scopus, Web of Science and Scielo; in order to select experimental studies with early exposure to ethanol, with the outcome of behavioral changes. The PICO strategy was Population: wild type zebra fish; Intervention: in vivo exposure to ethanol during early development; Comparison: without exposure to alcohol or any other substance added to the embryos or medium, the same manipulation of the experimental group; Outcome: behavioral parameters; and study designs: primary, randomized studies. In summary this strategy, the selected articles needed at least one group as a control / naive, a group exposed only to ethanol, and at least one type of evaluation evaluated after a period of ethanol withdrawal to configure a FASD model. The quality of the studies was analyzed according to the SYRCLE Checklist. Results: The electronic search of scientific databases retrieved 1181 scientific articles. After applying the inclusion and exclusion criteria, 29 scientific manuscripts were eligible. The AB strain (59%) was the most frequently used as a FASD model, followed by TU and TU (17%). The period of exposure to ethanol used in the studies included the initial period of 2 hours postfertilization (hpf) to 9 days post-fertilization, with the period of 2-24 hpf being the most used (43%). The 1% ethanol concentration was the most frequently used (57%) to induce zebrafish FASD models. Behavioral assessments took place in the short and long term; 30% of the experiments in the selected studies performed behavioral assessments in the larval phase (<10 dpf); 42% after the sexually mature phase (> 3 months). The larval phase was the most used to assess motor activity and anxious behavior. All approaches to sociability in adults have revealed deficits in this cognitive domain as a lasting effect. Aggressive behavior was persistently increased as an effect of early continuous exposure to 1% ethanol, while more punctual and mild exposure to ethanol had no effect on aggressive behavior. Learning and memory have been impaired in adult zebrafish treated with ethanol. Early exposure to ethanol promoted greater habituation in zebrafish tested in the conditioning preference place (CPP), which was related to susceptibility to addiction. Conclusion: The studies analyzed in this systematic review suggest that early exposure to ethanol in the embryonic phase alters the behavior of zebrafish in the fields of learning, memory, sociability and anxiety, similar to the changes found in FASD in humans. These findings are better identified in the adult phase of zebrafish, and it is important to develop more appropriate tools for the study in earlier stages of development, as well as the use of standardized guidelines such as the ARRIVE guide in the search for greater transparency, reproducibility and reliability of studies.