Investigation into the effects of pregabalin on motor nerves and their underlying mechanisms

Pregabalin, a typical representative of pharmaceuticals and personal care products (PPCPs), has seen its environmental residue issue become increasingly prominent due to its widespread and high-volume clinical use. While its potential neurotoxic risks have attracted attention, the specific mechanisms underlying its induction of neurotoxicity have not yet been fully elucidated. This study investigated the neurotoxic effects of pregabalin using a zebrafish model: first, it predicted the potential mechanisms and key targets of pregabalin-induced neurotoxicity utilizing network toxicology techniques, followed by verification via experimental methods such as reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results showed that pregabalin exposure binds to key receptors such as GRIA2, interferes with the glutamatergic synaptic pathway, thereby triggering neuronal apoptosis, and ultimately leading to neurodevelopmental impairment in zebrafish larvae - specifically a significant 8.8% reduction in neural axon length, accompanied by abnormal motor behavior, namely a significant 33.3% decrease in movement distance and a 33.4% decrease in movement speed, respectively. These findings not only provide key experimental evidence for the in-depth analysis of the neurotoxic effects and molecular mechanisms of environmental pregabalin exposure but also offer theoretical support for the systematic assessment of its eco-neurotoxic risks to ecosystems.