PCB153 induces epileptic-like behaviors in zebrafish by disrupting the GABA pathway

Abstract

Polychlorinated biphenyls (PCBs), as persistent organic pollutants, have raised widespread concerns regarding their environmental and biological impacts. This study aims to investigate the effects of PCB153 exposure on the zebrafish nervous system, particularly its potential mechanism in inducing epileptic-like behaviors. Zebrafish at 6 h post-fertilization (hpf) were exposed to PCB153 solutions at concentrations of 1 μM, 5 μM, and 10 μM via waterborne exposure. The results indicated that PCB153 exposure significantly altered zebrafish locomotor activity and light/dark transition behaviors, with a marked presence of epileptic-like behaviors, especially in the high-concentration groups (5 μM and 10 μM). Further molecular analysis revealed that PCB153 exposure led to alterations in the expression of genes related to the GABAergic signaling pathway, particularly the upregulation of gad2 and the downregulation of GABA receptor genes. These findings suggest that PCB153 may disrupt the GABA system, resulting in an imbalance between excitation and inhibition in the nervous system, thus triggering epileptic-like behaviors. Additionally, treatment with SAHA (histone deacetylase inhibitor) showed neuroprotective effects, alleviating the epileptic-like behaviors induced by PCB153. Transcriptome sequencing further identified extensive changes in gene expression, predominantly in pathways associated with neuronal function and development. In conclusion, PCB153 exposure disrupts the GABAergic neurotransmitter system, which may be a key mechanism underlying the epileptic-like behaviors in zebrafish, and SAHA treatment could potentially have therapeutic effects. This study provides new insights into the toxic effects of environmental pollutants on the nervous system and offers experimental evidence for future neuroprotective strategy research.