title: PCB153 (2,2',4,4',5,5'-hexachlorobiphenyl) differentially affects the VEGF/VEGFR system depending on photoperiod in the ovine choroid plexus.
abstract: 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: 1200pg/ml) than during long days (LD: 200pg/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 (0.3mg/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.
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczepkowska
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lagaraine
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Robert
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Młynarczuk
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Dufourny
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Thiéry
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland. Electronic address: j.skipor@pan.olsztyn.pl.
authors.forename: Janina
authors.initials: J
authors.lastname: Skipor
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol; D005260:Female; D017440:Photoperiod; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D040262:Receptors, Vascular Endothelial Growth Factor; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: Choroid plexus; Ewes; Photoperiod; Polychlorinated biphenyls; Vascular endothelial growth factor