Developmental exposure to the A6-pesticide causes changes in tyrosine hydroxylase gene expression, neurochemistry, and locomotor behavior in larval zebrafish

Abstract

\n In recent years, the increase in the synthesis of biopesticides for alternative agricultural uses has necessitated the study of their impacts. Among these compounds, several of them are known to exert endocrine-disrupting effects causing deregulation of a variety of physiological functions affecting cell signaling pathways involved in neural cell differentiation leading to developmental neurotoxicity. In this current paper, we thus determined the impact of the biopesticide A6 on zebrafish larvae, which is structurally linked to estrogenic endocrine disruptors. The objective of this study was to define the toxicity of A6, the mechanisms responsible, and to evaluate its effects on the locomotor activity at nanomolar concentrations (0, 0.5, 5, and 50 nM). We show through its blue fluorescence properties that A6 accumulates in different parts of the body as intestine, adipose tissue, muscle, yolk sac and head. We display also that A6 disrupt the development and affects the function of the central nervous system, especially the expression of tyrosine hydroxylase (TH) in dopaminergic neurons. We studied whether A6 disturbs the target genes expression and recorded that it downregulated genes embroiled in TH expression, suggesting that A6’s neurotoxic effect may be the result of its binding propinquity to the estrogen receptor.