Date Published: February 11, 2019
Publisher: Public Library of Science
Author(s): Katarzyna Nierwińska, Marta Nowacka-Chmielewska, Jacek Bernacki, Sławomir Jagsz, Małgorzata Chalimoniuk, Józef Langfort, Andrzej Małecki, Michal Toborek.
The present study aimed to estimate the effect of endurance training, two doses of testosterone, and the combination of these stimuli on the level of the endothelial proteins claudin, occludin, JAM-1, VE-cadherin, ZO-1, ZO-2, and P-glycoprotein in rat spinal cords. Adult male Wistar rats were trained using a motor-driven treadmill for 6 weeks (40–60 min, 5 times per week) and/or were treated for 6 weeks with two doses of testosterone (i.m.; 8 mg/kg or 80 mg/kg body weight). Spinal cords were collected 48 hours after the last training cycle and stored at -80°C. The levels of selected proteins in whole tissue lysates of the spinal cord were measured by western blot. Testosterone-treated trained rats had significantly lower claudin levels than vehicle-treated trained rats. High doses of testosterone resulted in a significant decrease in claudin-5 in untrained rats compared to the control group. Both doses of testosterone significantly reduced occludin levels compared to those in vehicle-treated untrained rats. The JAM-1 level in the spinal cords of both trained and untrained animals receiving testosterone was decreased in a dose-dependent manner. The JAM-1 level in the trained group treated with high doses of testosterone was significantly higher than that in the untrained rats treated with 80 mg/kg of testosterone. VE-cadherin levels were decreased in all groups receiving testosterone regardless of endurance training and were also diminished in the vehicle-treated group compared to the control group. Testosterone treatment did not exert a significant effect on ZO-1 protein levels. Testosterone and/or training had no significant effects on ZO-2 protein levels in the rat spinal cords. Endurance training increased P-glycoprotein levels in the rat spinal cords. The results suggest that an excessive supply of testosterone may adversely impact the expression of endothelial proteins in the central nervous system, which, in turn, may affect the blood-brain barrier function.
The blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) play important roles in protecting the central nervous system (CNS) from the influence of external factors such as hormones and xenobiotics. Alterations to the barrier integrity are directly involved in the trafficking of inflammatory cells into the brain and in the development of neuroinflammatory responses. The BBB and the BSCBs are not only physical barriers, but they also control influx and efflux transport as well as contain the drug-metabolizing enzymes. Certain bioactive substances, including toxic substances, may lead to disorders affecting the function of the BBB and BSCB. Together, the BBB and BSCB are important conduits and interfaces in humoral-based communication between the CNS and the rest of the body .
The images obtained by the western blot method are presented in the collective figure (Fig 1).
The proper functioning of the BSCB depends upon tight junctions which are specialized proteins responsible for the maintenance of a solid structure. Among the most significant, are the tight junctions (TJs) between cells (built by the proteins ZO-1, ZO-2, claudin-5, and occludin) and the adhesion junctions (constituted e.g. by VE-cadherin). The effects of AR ligands on the TJs in CNS vessels have not yet been studied .