The effect of endurance training and testosterone supplementation on the expression of blood spinal cord barrier proteins in rats

Abstract

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.

Androgens’ effects on cerebrovascular function in health and disease

“…The increase in BBB permeability after depletion of T is due to loss of expression of tight junction proteins such as claudin-5 and ZO-1 [37]. Conversely, a recent study shows that T supplementation for 6 weeks to young adult male Wistar rats compromises the blood spinal cord barrier as shown by a reduced expression of tight junction proteins, such as occludin, Jam 1, and VEcadherin in the spinal cord [38]. This indicates that androgens' effects on the blood barrier could be regionspecific.…”

Fetal glucocorticoid exposure leads to sex‐specific changes in drug‐transporter function at the blood‐brain barrier in juvenile guinea pigs

“…In human and mouse renal cell culture, estradiol increased digoxin clearance, and P‐gp/ Abcb1 expression, while testosterone had no effect 57 . However, at the blood‐spinal cord barrier of rats, testosterone supplementation in vivo led to increased P‐gp protein expression 58 . In male guinea pigs, testosterone levels during the post‐natal androgen surge peak at around PND3 59 ; it is possible that high levels of testosterone have a positive regulatory effect on P‐gp, leading to sexual dimorphism in transporter expression and function.…”

“…57 However, at the blood-spinal cord barrier of rats, testosterone supplementation in vivo led to increased P-gp protein expression. 58 In male guinea pigs, testosterone levels during the post-natal androgen surge peak at around PND3 59 ; it is possible that high levels of testosterone have a positive regulatory effect on P-gp, leading to sexual dimorphism in transporter expression and function. There is a wide range of evidence supporting sex differences in drug metabolism in adults, 60 however, literature in the neonate is scarce.…”

Disruption of neurosteroid synthesis and release by tris(2,3‐dibromopropyl)isocyanurate in primary mouse cortical astrocytes in vitro

“…In addition, Chen et al (2011) suggested that T had a detrimental effect following intracerebral hemorrhage‐induced brain injury in rats. Nierwińska et al (2019) have found that the excessive supply of T may have an adverse effect on the expression of endothelial proteins in the nervous system, which in turn may affect the functioning of the blood–brain barrier. As in the case of T, too low or too high a concentration of E 2 induces the process of apoptosis in cells (Harms et al, 2001).…”