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
Introduction
Polychlorinated biphenyls (PCBs) are the most persistent and ubiquitous 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 abundant in the environment, constitute a large part of the PCB residue detected in animal tissues and have been reported to accumulate preferentially 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 photoperiod 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 barrier (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 associated with several scaffolding and regulatory cytoplasmic proteins, including 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 expression levels in the blood–brain barrier under in vitro (Eum et al., 2008) and in vivo conditions (Seelbach et al., 2010). Therefore, we hypothesised that PCB153 could alter TJ expression in the ovine CP in a photoperiod-dependent manner. To address this hypothesis we studied the effect of PCB153 treatment during SD and LD on the expression of TJ proteins in the CP in ewes.
Section snippets
Animals and experimental design
The experiment was conducted in accordance with Authorisation No. 37801 for Animal Experimentation and Surgery from the French Ministry of Agriculture following the European Community Council Directive 86/609/EEC and approved by the “Val de Loire” Local Ethics committee. Indoor light treatments, surgery and postoperative care were conducted in certified facilities (ISO 9001/2000 version, July 2006, No. B37-175-2). Studies were performed on Ile-de-France ewes (n = 28; 2.5 years old, the same used
Results
Sixteen days of exposure to low doses of PCB153 resulted in a significant decrease in the expression of some TJ proteins in the CP during SD but not during LD. The densitometry results are presented in Fig. 2 for SD and in Fig. 3 for LD. PCB153 treatment significantly decreased the expression of the transmembrane TJ-protein claudin-1 (Fig. 2b). Its expression was 50-fold lower in PCB-treated animals compared to vehicle-treated ewes (median = 0.01, min = 0.0004 and max = 0.03 in SD-PCB group, and
Discussion
The present study represents the first attempt to evaluate the impact of photoperiod on the effect of PCB153 on TJ proteins that regulate blood–CSF barrier function in adult ewes. The results presented demonstrate that the same dose of PCB153 given to ewes maintained under artificial LD or SD conditions does not induce the same effect on TJ protein expression levels in the CP. PCB153 affected TJ protein expression only during SD. In our previous work (Skipor et al., 2012) we demonstrated that
Conflict of interest statement
Nothing declared.
Acknowledgments
This work was supported by the Ministry of Science and Higher Education, Poland, by Grant No. 258/N-INRA/2008/0 and French INRA Grant No. DWM/N19/INRA/2008. Participation of A.S. was supported by the European Union within the European Social Fund and V.R. by FP7 Project “REFRESH” 264103.
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These authors contributed equally to this work.