Activation of the MKK4/7-JNK-c-Jun axis mediates bisphenol F-induced neurodegeneration and behavioural alteration in adult zebrafish.

Bisphenol F (BPF), widely utilised as an industrial substitute for bisphenol A (BPA), has recently surfaced as a global environmental pollutant owing to its chemical stability, vast application, and rising identification throughout several ecological compartments. Notwithstanding its reputation as a safer alternative, emerging data indicates that BPF may produce similar or even more pronounced toxicological consequences. This study found that adult zebrafish exposed to environmentally relevant concentrations of BPF displayed significant anxiety-like behaviour, diminished cognitive performance, and decreased scototaxis preference, indicating increasing neurobehavioral dysfunction. These behavioural changes suggest that prolonged BPF exposure disrupts neuronal circuit integrity and emotional regulation. Biochemical tests indicated a significant decline in total antioxidant capacity, coupled with diminished activities of catalase and superoxide dismutase, as well as increased levels of lipid peroxidation. This array of alterations indicates significant oxidative stress and impaired antioxidant defence mechanisms in the zebrafish brain. At the molecular level, a duration-dependent activation of the MKK4/7-JNK-c-Jun signalling cascade was noted, aligning with the onset of pro-apoptotic MAPK pathways under oxidative circumstances. Supporting these findings, histological evaluations verified significant neuronal loss and chromatin condensation, especially in the periventricular grey matter, a region essential for adult neurogenesis. Collectively, our findings suggest that extended exposure to BPF triggers oxidative stress-mediated apoptotic signalling, resulting in neurodegeneration and notable behavioural deficits. This study highlights the pressing necessity to reevaluate the environmental safety and regulatory oversight of BPF, considering its widespread application and proven ability to impair vertebrate neurological health.