Integrated behavioral, transcriptomic and metabolomic analysis reveals the neurotoxicity of trichloroethylene in adult zebrafish (Danio rerio)

Trichloroethylene (TCE), a persistent environmental pollutant, poses potential health risks through multiple exposure routes, such as inhalation of vapor-phase TCE or ingestion of contaminated water and food. While recognized as a carcinogen, its neurobehavioral effects remain poorly characterized. This study investigated the mechanisms of TCE neurotoxicity in adult zebrafish following chronic exposure to environmentally relevant concentrations (20, 60, and 180 μg/L). Behavioral assessments revealed concentration-dependent anxiety-like behavior, reduced exploration, and memory impairment. Transcriptomic analysis identified progressive disruption of visual perception, synaptic signaling, and ion channel activity pathways. Building on this, we validated the expression of key genes by qPCR: gabrr3a (a GABA receptor subunit) was significantly upregulated in the 60 μg/L group, which was highly correlated with anxiety-like behaviors; cryba1b (a crystallin protein) showed a non-monotonic expression pattern, while lim2.1 (a lens membrane protein) exhibited a highly significant dose-dependent upregulation with increasing concentrations, indicating that the visual system is a sensitive target of TCE toxicity. Metabolomic profiling showed altered amino acid metabolism at low concentrations and severe energy metabolism suppression with inflammatory activation at high concentrations. The integrated multi-omics approach demonstrates that TCE induces neurobehavioral deficits through coordinated disruption of neural function and metabolic homeostasis, highlighting visual system impairment as a novel sensitive endpoint. These findings provide new insights into TCE's ecological risk and mechanistic toxicity. • First integration of behavior, transcriptomics and metabolomics to decode TCE neurotoxicity. • Multi‑omics reveals a shift from synaptic & visual pathway alterations to systemic metabolic suppression. • Dose-dependent gene dysregulation ( lim2.1, gabrr3a, cryba1b ) links molecular changes to anxiety and cognitive decline. • This study provides mechanistic evidence for revising risk assessment of TCE in aquatic environments.