Effects of subchronic exposure of perfluorooctane sulfonate on cognitive function of mice and its mechanism*

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant, and its potential impact on cognitive function remains unclear. We adopted the C57BL/6J mouse model to investigate the effect of PFOS on cognitive function, as well as the underlying mechanisms. Subchronic exposure was performed by administering PFOS via drinking water for 6 months (at doses of 0, 0.2, and 2.0 mg/kg/day), starting from 10.5 months old. The object recognition ability was tested at 2, 4, and 6 months of exposure, and spatial learning and memory were assessed at endpoint. The apoptosis of neurons and astrocytes in the cortex and hippocampus was analyzed, as well as the potential apoptotic signaling pathways. Our results showed that exposure to PFOS for 6 months caused a decrease in object recognition ability and a decline in learning and spatial memory. PFOS selectively increased apoptosis in neurons of the cerebral cortex and specifically activated the endoplasmic reticulum stress PERK/CHOP signaling pathway. In conclusion, our results confirmed that subchronic exposure to PFOS can lead to cognitive impairment in mice, which might be closely associated with the specific activation of an endo-plasmic reticulum stress-induced pro-apoptosis pathway in the cerebral cortex neurons.

Automated summary

This study investigated the impact of PFOS on cognitive function and the underlying mechanisms using a C57BL/6J mouse model. The results showed that exposure to PFOS for 6 months caused a decline in object recognition ability, learning, and spatial memory. Furthermore, PFOS selectively increased apoptosis in neurons of the cerebral cortex and activated the endoplasmic reticulum stress PERK/CHOP signaling pathway. These findings suggest that subchronic exposure to PFOS can lead to cognitive impairment in mice, which may be associated with the specific activation of an endoplasmic reticulum stress-induced pro-apoptosis pathway in cerebral cortex neurons.