PCB153 (2,2′,4,4′,5,5′-hexachlorobiphenyl) differentially affects the VEGF/VEGFR system depending on photoperiod in the ovine choroid plexus
Résumé
Ortho-substituted polychlorinated biphenyls (PCBs) preferentially accumulate in the brain and cerebrospinal fluid (CSF) compared with other PCBs. We previously demonstrated in ewes that an identical dose of PCB153, the most environmentally prevalent congener, resulted in a higher plasma concentration during short days (SD: 1200 pg/ml) than during long days (LD: 200 pg/ml). Moreover, PCB153 treatment only reduced the SD tight junction protein content in the choroid plexus (CP), which was followed by a significant increase of the PCB153 concentration in the CSF. The aim of the present study was to evaluate how PCB153 treatment affects the VEGF/VEGFR system that maintains CSF homoeostasis and CP function. To do so, we collected CPs from ovariectomised, oestradiol-replaced adult ewes maintained under artificial LD or SD and treated them per os with low doses of PCB153 (0.3 mg/kg, 3 times a week for 3 weeks). Exposure to PCB153 significantly affected (P<0.05) the VEGF/VEGFR system during the SD period, provoking increases in VEGF164 mRNA and protein levels and decreases in VEGFR-1 mRNA levels and VEGFR-2 mRNA and protein levels. These results suggest that exposure to environmentally relevant dose of PCB153 affects the VEGF/VEGFR system, which is involved in the fenestration of the CP endothelium and therefore in CSF production.