Perinatal Exposure to the Neonicotinoid Thiacloprid Impacts Transcription of Neuroplasticity and Neuroendocrine Markers in Mice but Not in the Zebrafish Model

Abstract

Neonicotinoids are widely used insecticides in agriculture, aquaculture, pet care, and urban pest control. Initially developed to selectively target the insect cholinergic system, their extensive use has raised concerns about adverse effects on nontarget vertebrates. This study investigated the developmental neurotoxicity of the neonicotinoid thiacloprid using two vertebrate models: zebrafish and mice. Transgenic cyp19a1b-GFP zebrafish eleutheroembryos, which report estrogenic activity, were exposed to thiacloprid (10−6–10−8 M) for 4–5 days. No significant changes were observed in GFP expression or neuroplasticity and neuroendocrine markers, suggesting a limited impact in this aquatic model. In contrast, prenatal exposure of mice to thiacloprid (0.06, 0.6, or 6 mg/kg/day from embryonic day 6.5 to 15.5) produced dose-, sex-, and region-specific alterations in brain gene expression during adolescence (postnatal day 35). At low to mid doses, markers of neurogenesis and plasticity, such as doublecortin in the amygdala, neurogenin, nestin, and PCNA in the hippocampus and cerebellum, were upregulated. However, high-dose exposure (6 mg/kg/day) led to reduced expression of these markers, including BDNF in the hypothalamus and PCNA in the hippocampus, particularly in females. These results indicate that thiacloprid, even at low doses, can subtly but significantly affect mammalian brain development. Further research is needed to assess the neurodevelopmental risks of neonicotinoids in vertebrates, including humans.