Acute low-dose benzo[a]pyrene exposure induces neurodegenerative syndrome in cyp1a low-expression zebrafish: A novel living Bioindicator for dioxin-like environmental pollutants

Abstract

Benzo[a]pyrene (BaP), a ubiquitous environmental polycyclic aromatic hydrocarbon (PAH), elicits toxicity that is closely linked to the activity of the key metabolic enzyme CYP1A. In this study, a cyp1a low-expression zebrafish strain, KI (cyp1a^+/+-T2A-mCherry), was used to investigate the toxic effects and mechanisms of low-dose BaP exposure under conditions of cyp1a deficiency. The results revealed that cyp1a low expression significantly exacerbated BaP-induced mortality, growth inhibition, apoptosis, and oxidative stress. It also induced neurodegenerative lesions accompanied by reduced acetylcholine (ACh) levels. Behavioral assessments showed that cyp1a low expression zebrafish displayed anxiety-like behaviors, altered locomotor activity, and visual impairment following exposure-effects potentially associated with the down regulation of opsin genes (e.g., opn1sw1, opn1sw2). Transcriptomic profiling further identified substantial differences in gene expression between cyp1a low expression and wild-type zebrafish after BaP treatment. KEGG pathway analysis highlighted enrichments related to neurodegenerative diseases, cell cycle arrest, and apoptosis in the cyp1a low expression group, along with dysregulated expression of neurodegeneration-associated genes such as APPa, APPb, PSEN2, and TUBB. Notably, this study is the first to report that cyp1a low expression exhibit enhanced behavioral sensitivity to trace levels of dioxin-like contaminants (10⁻¹³ M TCDD). When exposed to polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), this model demonstrated pronounced and quantifiable changes in locomotor behavior, underscoring its potential as a highly sensitive novel biosensor for environmental monitoring. Overall, this work not only confirms that cyp1a deficiency markedly increases susceptibility to BaP-induced neurodegeneration in zebrafish but also establishes the cyp1a low-expression model as a transformative tool offering novel biomarkers for risk assessment and early warning of dioxin-like pollutants. It significantly advances the sensitivity and specificity of environmental toxicology research, providing new technical and theoretical foundations for the field.

Keywords: BaP; Cyp1a; Dioxin-like pollutants; Neurodegenerative effects; Toxicology.