Perfluorooctane sulfonate disrupts the blood brain barrier through the crosstalk between endothelial cells and astrocytes in mice

Perfluorooctane sulfonate (PFOS), a classic environmental pollutant, is reported to accumulate in brain and induce neurotoxicity. However, little is known the route and mechanism of its entrance in brain. In the present study, ICR mice were treated with PFOS for 28 days, the cerebral PFOS were measured and the morphological and ultrastructural changes of blood-brain barrier (BBB) were observed. Also, the expression and localization of the proteins related to the cerebral damages, tight junctions (TJs) and p38 activation were detected. Additionally, U87 cells were used to explore the role of p38 in PFOS-induced damages of astrocytes. PFOS significantly decreased the expression of TJ-related proteins (ZO-1, Claudin-5, Claudin-11, Occludin) in endothelial cells and disrupted BBB, which subsequently led PFOS to astrocytes and increased the expression of the proteins related to astrocytic damages (Aquaporin 4 and S100 beta). These results aggravated BBB disruption and further increased the cerebral PFOS levels. Besides, phosphorylated p38 activation was involved into PFOS-induced astrocytic damages in vivo and in vitro. In conclusion, the crosstalk between endothelial cells and astrocytes facilitated the BBB disruption and increased the accumulation of PFOS in brain. Our findings provided a new insight into the toxicological and physiological profiles of PFOS-induced neurotoxicity. (C) 2019 Elsevier Ltd. All rights reserved.