Bioindicadores do transtorno do espectro alcoólico fetal: como o zebrafish (Danio rerio) pode ajudar?

Abstract

Ethanol consumption by pregnant women can lead to a set of clinical manifestations in fetuses as a result of embryonic exposure to ethanol known as Fetal Alcohol Spectrum Disorder (FASD). This neurodevelopmental disorder presents various behavioral and cognitive phenotypes depending on the concentration, persistence and period of exposure to ethanol. Its behavioral manifestations resemble other neuropsychiatric conditions, such as Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder, which can lead to diagnostic confusion and mistaken treatment. The aim of this study was to investigate biological indicators, both behavioral and molecular, for ASD. We used the zebrafish (Danio rerio), a small freshwater fish with high genetic homology with humans, as a model to investigate the effects of embryonic exposure to ethanol on behavior, cognition and gene expression patterns. We exposed 24-hour post-fertilization AB zebrafish embryos for two hours to three concentrations of ethanol (0.0%, 0.5% and 1.0%). In order to observe the effect of embryonic exposure at different stages throughout ontogeny, we carried out behavioral analyses - using the Free Movement Pattern test in a Y maze - and molecular analyses - using gene expression by qPCR - with the animals at the fry (15 days post fertilization, dpf), juvenile (45 dpf) and adult (90 dpf) stages. Our results showed hypolocomotion in the fry stage and hyperlocomotion in the juvenile and adult stages, as well as cognitive impairment in the latter two stages in individuals exposed to low concentrations of ethanol, evidenced by an increase in repetitive pattern movements and a reduction in the alternation strategy. As for the molecular markers evaluated, the results indicate a significant deficit in the expression of most of the genes studied in the fry and adult stages, but not in the juveniles. Behavioral and molecular assessments in zebrafish exposed to ethanol during the embryonic period will help to elucidate the cognitive and physiological alterations involved in FASD.