Effect of acute or subchronic stress on T cell response in peripheral blood: Regulatory role of vitamin D

The immune response, orchestrated by helper (Th1, Th2, and Th17) and regulatory (Treg) T cells, is modulated by stress and Vitamin D (Vit-D). Although the immunomodulatory functions of both are known, their specific roles on Th cells have not been fully clarified, yet. On this background, we aimed to investigate the effect of acute or subchronic stress on the distribution of peripheral T lymphocytes, as well as the immunomodulatory role of Vit-D. Young adult male, Swiss-albino mice (30–40g) were allocated to the control, acute stress (AS), subchronic stress (ChS), control+Vit-D, AS+Vit-D, and ChS+Vit-D groups (n=11/group). The combined cold (2-h at 4°C)-immobilization (2-h in a restrainer) stress protocol was employed as one day in AS groups and five consecutive days in ChS groups. Vit-D (2μg/kg ip) was applied every other day, until the end of the protocol. Serum cortisol, Vit-D and cytokine levels (IL-4, IFN-γ, and IL-17A) were measured, and lymphocytes from blood samples were subtyped by flow-cytometry. Stress exposure caused differential Th and Treg responses, acute stress shifting the response to Th1, and subchronic stress shifting the response to Th2. Th17 and Treg cells were lower in subchronic stress exposed mice. These changes became comparable to control values in Vit-D treated groups. The T cell response, crucial for immune system function, differs on the basis of stress exposure as such the Vit-D treatment. The tolerogenic profile created by Vit-D should be considered for management of stress-related diseases. Our results may help to provide a better understanding of disease pathogenesis

Effect of acute or subchronic stress on T cell response in peripheral blood: Regulatory role of vitamin D

14-24The immune response, orchestrated by helper (Th1, Th2, and Th17) and regulatory (Treg) T cells, is modulated by stress and Vitamin D (Vit-D). Although the immunomodulatory functions of both are known, their specific roles on Th cells have not been fully clarified, yet. On this background, we aimed to investigate the effect of acute or subchronic stress on the distribution of peripheral T lymphocytes, as well as the immunomodulatory role of Vit-D. Young adult male, Swiss-albino mice (30–40g) were allocated to the control, acute stress (AS), subchronic stress (ChS), control+Vit-D, AS+Vit-D, and ChS+Vit-D groups (n=11/group). The combined cold (2-h at 4°C)-immobilization (2-h in a restrainer) stress protocol was employed as one day in AS groups and five consecutive days in ChS groups. Vit-D (2μg/kg ip) was applied every other day, until the end of the protocol. Serum cortisol, Vit-D and cytokine levels (IL-4, IFN-γ, and IL-17A) were measured, and lymphocytes from blood samples were subtyped by flow-cytometry. Stress exposure caused differential Th and Treg responses, acute stress shifting the response to Th1, and subchronic stress shifting the response to Th2. Th17 and Treg cells were lower in subchronic stress exposed mice. These changes became comparable to control values in Vit-D treated groups. The T cell response, crucial for immune system function, differs on the basis of stress exposure as such the Vit-D treatment. The tolerogenic profile created by Vit-D should be considered for management of stress-related diseases. Our results may help to provide a better understanding of disease pathogenesis

The Effect of Hypercholesterolemia on the Contractions of Detrusor Strips in Response to Neural Stimulation in Rats

Aim: To investigate the effect of hypercholesterolemia on in vitro contractions of the detrusor smooth muscle stimulated by an electrical field in rats and the relative contributions of cholinergic and noncholinergic neurotransmission. Materials and methods: Sprague-Dawley rats were fed with standard diet (NC group) or with 4% cholesterol diet (HC group). After 4 weeks, the urinary bladder was excised under anesthesia and 4 detrusor strips were prepared. Blood samples were collected for serum lipid profile, and aortic arches were dissected for histopathological examination. In vitro contractile function of the detrusor smooth muscle was evaluated with: 1) electrical field stimulation (EFS) only, 2) EFS in the presence of muscarinic antagonist atropine (10-6 M), and 3) EFS in the presence of atropine and P2X antagonist phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate (10-4 M) or P2X agonist alpha,beta-methylene-adenosine-5'-triphosphate (10-5 M). Results: Plasma cholesterol was elevated in the HC group (P < 0.05); there was no sign of atherosclerosis. Although EFS-induced contractions were higher in the HC group, the difference was not significant. Cholinergic or purinergic antagonists decreased contractile response by desensitization with the purinergic agonist. The contribution of cholinergic and purinergic components were also similar in both groups. Conclusion: The contribution of cholinergic and noncholinergic mechanisms of neurotransmission seems to be independent of the high cholesterol content of the diet and the plasma cholesterol level in rat detrusor muscle.WoSScopu

Effect of Transient Maternal Hypotension on Apoptotic Cell Death in Foetal Rat Brain

Background: Intrauterine perfusion insufficiency induced by transient maternal hypotension has been reported to be associated with foetal brain malformations. However, the effects of maternal hypotension on apoptotic processes in the foetal brain have not been investigated experimentally during the intrauterine period. Aims: The aim of this study was to investigate the effects of transient maternal hypotension on apoptotic cell death in the intrauterine foetal brain. Study Design: Animal experimentation. Methods: Three-month-old female Wistar albino rats were allocated into four groups (n=5 each). The impact of hypoxic/ischemic injury induced by transient maternal hypotension on the 15th day of pregnancy (late gestation) in rats was investigated at 48 (H17 group) or 96 hours (H19 group) after the insult. Control groups underwent the same procedure except for induction of hypotension (C17 and H17 groups). Brain sections of one randomly selected foetus from each pregnant rat were histopathologically evaluated for hypoxic/ischemic injury in the metencephalon, diencephalon, and telencephalon by terminal transferase-mediated dUTP nick end labelling and active cysteine-dependent aspartate-directed protease-3 (caspase-3) positivity for cell death. Results: The number of terminal transferase-mediated dUTP nick end labelling (+) cells in all the areas examined was comparable in both hypotension and control groups. The H17 group had active caspase-3 (+) cells in the metencephalon and telencephalon, sparing diencephalon, whereas the C19 and H19 groups had active caspase-3 (+) cells in all three regions. The number of active caspase-3 (+) cells in the telencephalon in the H19 group was higher compared with the metencephalon and diencephalon and compared with H17 group (p<0.05). Conclusion: Our results suggest that prenatal hypoxic/ischemic injury triggers apoptotic mechanisms. Therefore, blockade of apoptotic pathways, considering the time pattern of the insult, may constitute a potential neuroprotective approach for the detrimental effects of prenatal hypoperfusion.Wo