Behavioral and Developmental Effects of Lead Acetate Exposure in Embryonic Zebrafish

Abstract

Despite lead’s ban several decades ago, it remains a public health threat due to its persistent nature. Zebrafish are highly effective for modeling several disorders, particularly those affecting neurological and cognitive functions, and are well-suited for assessing the impact of environmental toxins like lead. This study aimed to investigate the behavioral and developmental effects of embryonic lead exposure using the zebrafish (AB strain) model system. Embryos were exposed to lead acetate (PbAc) at concentrations ranging from 0.3 to 0.7 µg/ml using an exposure window of 6 to 48 hours postfertilization. Lead acetate exposure induced dose-dependent teratogenic effects, such as spinal kinks, spinal curvatures, beaky mouths and uninflated swim bladder. Behavioral assessments conducted at 3- and 7-days post fertilization (dpf) revealed significant behavioral alterations. At 3 dpf, spontaneous circle swimming behavior suspected to be seizure-like was observed in lead-exposed group and was more pronounced under light conditions in a dose-dependent manner. A calcium biosensor assay validated this seizure-like behavior, revealing a general increase in fluorescence intensities in lead-treated groups compared to controls. Electrophysiological recordings confirmed that larvae exhibiting circle swimming behavior had heightened neural activity, indicating a potential seizure-like phenotype driven by lead exposure. At 7 dpf optomotor response assay, suggested altered response in the optomotor response of lead-exposed larvae and light/ dark locomotor testing showed reduced motor activity levels, particularly in the dark. Thigmotaxis assays did not show any significance in anxiety-like behaviors between control and lead treated groups. Overall, our findings suggest that early-life lead exposure leads to morphological defects, behavioral alterations and seizure susceptibility, enhancing our understanding of lead’s neurotoxic potential during early development.