Effect of a two-week treatment with a low dose of 2,2′4,4′,5,5′-hexachlorobiphenyl (PCB153) on tight junction protein expression in ovine choroid plexus during long and short photoperiods Aleksandra Szczepkowska a, 1 , Christine Lagaraine b, 1 , Vincent Robert b , Laurence Dufourny b , Jean-Claude Thiéry b , Janina Skipor a, ⁎ a Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland b INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380, Nouzilly, France abstract article info Article history: Received 29 January 2013 Received in revised form 27 March 2013 Accepted 28 March 2013 Available online 6 April 2013 Keywords: Polychlorinated biphenyls Tight junctions Blood–cerebrospinal fluid-barrier Choroid plexus Photoperiod Ewes Ortho-substituted polychlorinated biphenyls (PCBs) preferentially accumulate in the brain and cerebrospinal fluid (CSF) compared to other PCBs. We previously reported that the same dose of 2,2′,4,4′,5,5′- hexachlorobiphenyl (PCB153) induced higher concentrations in the CSF of treated animals compared to controls during short days (SD), while no differences were observed during long days (LD). Similarly, the plasma concen- tration of PCB153 in treated ewes was higher during SD than LD. To understand the structural and molecular events explaining the photoperiodically different concentration of PCBs in the CSF in sheep, we studied the effect of photoperiod on PCB153 action on tight junction (TJ) protein expression in the choroid plexus (CP) of ewes. For that purpose, we collected CP from ovariectomised, estradiol-treated ewes maintained under artificial LD or SD and orally administered with a low dose (0.33 mg/kg/day, 3 times per week for 3 weeks) of PCB153 or vehicle. Exposure to PCB153 affected TJ proteins only during SD, and the levels of claudin-1, zonula occludens-2 (ZO-2), and afadin (AF-6) were significantly lower when compared to vehicle-treated animals. No differences were ob- served for occludin, junctional adhesion molecule-1 (JAM-1), claudin-5, ZO-1 and ZO-3. There was no effect of PCB153 treatment on TJ-mRNA levels. These results indicate that PCB153 selectively alters TJ proteins in the ovine CP. These alterations appear to be associated with the level of PCB153 in the blood plasma, which is mod- ulated by the photoperiod. This study emphasises the importance of photoperiod in the susceptibility of adult sheep to PCBs. © 2013 Elsevier Inc. All rights reserved. 1. Introduction Polychlorinated biphenyls (PCBs) are the most persistent and ubiqui- tous environmental pollutants. Structurally, there are at least two distinct classes of PCBs, coplanar (non-ortho-substituted) and non-coplanar (ortho-substituted) congeners. Ortho-substituted PCBs, the most abun- dant in the environment, constitute a large part of the PCB residue detected in animal tissues and have been reported to accumulate prefer- entially in the brain and cerebrospinal fluid (CSF) during PCB exposure compared with other PCBs (Kodavanti et al., 1998; Takasuga et al., 2004). Five highly chlorinated PCB congeners (PCB138, PCB149, PCB153, PCB180 and PCB187) account for 64–67% of the total PCBs in the CSF, and PCB153 is the most abundant (Montie et al., 2009). Recently, we demonstrated that in ewes treated with a low dose (0.3 mg/kg) of PCB153, the concentration of PCB153 in the CSF was higher in treated animals than in controls during short days (SD) and no differences were observed during long days (LD), which suggests an effect of photo- period on PCB153 access to the CSF (Skipor et al., 2012). Direct access of molecules from the periphery to the CSF is limited by the blood–CSF bar- rier (Skipor and Triery, 2008). In contrast to the blood–brain barrier, where the endothelium of brain capillaries is sealed by occluding bands of tight junctions (TJs) to form a physical barrier between the brain tissue and blood, the capillaries of the choroid plexus (CP) are fenestrated, and the choroidal epithelium constitutes a passive characteristic of the blood– CSF barrier. The integrity, paracellular permeability, and polarisation of epithelial and endothelial cells depend on the expression of TJ proteins, which includes the integral transmembrane proteins occludin (Furuse et al., 1993), junctional adhesion molecule-1 (JAM-1, Martin-Padura et al., 1998) and claudins (Cld; Furuse et al., 1998). These proteins are asso- ciated with several scaffolding and regulatory cytoplasmic proteins, in- cluding zonula occludens proteins (ZOs) and afadin (AF-6) (Wolburg and Lippoldt, 2002). We previously demonstrated in the ovine CP that the expression of occludin, ZO-1, ZO-2 and AF-6 proteins as well as cadherin (adherens junction protein) were significantly higher under SD (Lagaraine et al., 2011). PCBs have been shown to alter TJ protein Neurotoxicology and Teratology 37 (2013) 63–67 ⁎ Corresponding author at: 10 Tuwima Str. 10-748 Olsztyn, Poland. Tel.: + 48 89 539 31 26; fax: +48 895 35 74 21. E-mail address: j.skipor@pan.olsztyn.pl (J. Skipor). 1 These authors contributed equally to this work. 0892-0362/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ntt.2013.03.061 Contents lists available at SciVerse ScienceDirect Neurotoxicology and Teratology journal homepage: www.elsevier.com/locate/neutera