Developmental exposure to environmental levels of sulfamethoxazole (SMX) leads to hyperactivity in zebrafish larvae by inducing oxidative stress and calcium dyshomeostasis

Antibiotic contamination has emerged as a major environmental concern, with sulfamethoxazole (SMX), a widely used sulfonamide antibiotic, representing one of the most persistent and bioactive pollutants in aquatic ecosystems. Increasing evidence suggests that SMX exerts neurotoxic effects in both experimental and clinical contexts, yet its developmental neurotoxicity and underlying mechanisms remain poorly understood. In this study, we used zebrafish as a vertebrate model to investigate the neurodevelopmental impact of SMX exposure at environmentally relevant levels. Developmental assessments revealed that SMX altered spontaneous movement behavior and heart rate in early-stage larvae. High-throughput behavioral profiling showed pronounced hyperactivity, social avoidance, and reduced scototaxis, indicative of early neurobehavioral disruption. In vivo twophoton imaging demonstrated significant alterations in microglial number and morphology following SMX