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The transformation of the Polish economy and its privatization have given rise to much controversy. The authors targeted only one aspect: how the process of privatization tackle an issue of environmental liabilities of enterprises i.e. how their environmental mortgage look like. They discuss the environmental liabilities of enterprises in relation to the method of privatization applied.
Increased level of corticoid hormons during stress results in activation of hippocampal mineralocorticosteroid receptors (MRs) and glucocorticoid receptors (GRs). Our earlier studies showed impairment of LTP in the dentate gyrus (DG) of mice after 3 daily sessions of brief (10 min) restraint stress and LTP augmentation after 14 and 21 daily sessions of immobilization. In contrast, 1 and 7 daily sessions of immobilization did not affect LTP level. We demonstrated that the GR antagonist RU38486 selectively blocks the effect of 3 sessions of restraint. In the present study we investigated whether the effects of repeated brief restraint stress are mediated by MRs. C57BL/6 male mice were exposed to the restraint, lasting 10 minutes, for 3 and 14 days. 1 hour before immobilization the animals were subcutaneously injected with the MR receptor antagonist spironolactone. Mice were sacrifi ced 24 h after the last exposure to restraint and hippocampal slices were prepared. Field excitatory postsynaptic potentials were evoked by the stimulation of the lateral perforant path and recorded from the molecular layer of the DG. LTP induction was attempted by applying 4 trains of high-frequency stimulation (HFS, 100 Hz, 1 s, repeated every 25 s). In both experimental groups immediately after HFS recorded responses were potentiated but 2 h later they were diminished relative to control. Thus, the present results show that spironolactone blocks LTP induction after 3 and 14 days of daily restraint.
BACKGROUND AND AIMS: Affective spectrum disorders are a group of affective-, anxiety-, and stress-related syndromes which present a number of overlapping features. These relatively common syndromes are potentially life threatening and are associated with a high morbidity and mortality of individuals in the developed countries. Stress has been shown to be an important factor in the pathophysiology of affective spectrum disorders. The aim of the present study was to determine how the repeated neck restraint stress influences the behavior of the mice. We tested whether effects of the repeated stress depend on the number of daily restraint sessions. We also measured blood levels of ACTH and corticosterone. METHODS: C57BL/6 male mice were exposed to 1, 3, 7, 14 or 21 daily neck restraint sessions lasting 10 minutes. Control animals were subjected to manual handling. On the next day after the last restraint or handling depressive-like symptoms were evaluated using the tail suspension test (TST) and anxiety-like behavior was examined using the elevated plus maze (EPM) and open field test (OF). Plasma levels of corticosterone and ACTH were measured using the immunoassay kits. RESULTS: The data obtained so far suggest that mice subjected to 3 neck restraint stress sessions display a significant increase in the immobility time in the TST and enhanced behavioral signatures of anxiety in EPM and OF. After 7, 14 and 21 restraint sessions we observed a gradual decline of the behavioral response to stress, however depressive and anxiety signs were still present. Behavioral consequences of restraint stress were correlated with alterations in the ACTH and corticosterone level. CONCLUSION: These results shed a light on physiological mechanisms of the stress response and may lead in future to new therapies for depressed and/or anxious patients. Support: Jagiellonian University (project SET), Polish National Science Center grant no. 2013/09/D/NZ4/00592
Long-term potentiation (LTP) and long-term depression (LTD) are two cellular models of synaptic plasticity. These phenomena can be modulated by stress. Stress is correlated with an increased release of glucocorticoids (GCs) from the adrenal cortex. GCs act via two receptor types, glucocorticoid receptors (GRs) and mineralocorticosteroid receptors (MRs) which are expressed in a high density in the dentate gyrus (DG). Here we studied whether single brief restraint stress affects LTP and LTD in the DG and if these effects are mediated by GR and MR receptors. C57BL/6 male mice were subjected to the restraint, lasting 10 minutes. 1 hour before immobilisation animals were subcutaneously injected with glucocorticoid receptor antagonist RU38486 or mineralocorticoid receptor antagonist spironolactone. Hippocampal slices were prepared immediately after the end of restraint. Field excitatory postsynaptic potentials (fEPSP) were evoked in the molecular layer of the DG by the stimulation of the lateral perforant path. LTP was induced by 4 trains of high-frequency stimulation (100 Hz, 1 s, repeated every 25 s). LTD was evoked by low-frequency stimulation (1 Hz, 15 min). In slices from stressed mice LTP was enhanced, but LTD was impaired. The data indicate that facilitatory effects of restraint on LTP are diminished by RU38486 and spironolactone indicating the involment of both GRs and MRs. Preliminary results suggest that the inhibitory effects of restraint on LTD are decreased by RU38486.
The role of prostaglandins and nitric oxide (NO), generated after peripheral lipopolysaccharide (LPS) administration, in the adaptation of hypothalamic-pituitary-adrenal (HPA) axis under stressful circumstances remains to be elucidated. The aim of the present study was to assess the effect of chronic repetitive restraint or social crowding stress on the involvememt of nitric oxide and prostaglandins in the LPS-induced pituitary-adrenocortical response. Male Wistar rats were restrained in metal tubes 2x10 min/day or crowded in cages for 7 days prior to treatment. All compounds were injected i.p., cyclooxygenase (COX) and nitric oxide synthase (NOS) inhibitors 15 min before LPS. Two hrs after injection LPS induced a significant increase in ACTH and corticosterone secretion. Repeated restraint impaired more potently than crowding stress the LPS-induced HPA-response. Indomethacin, a non-selective COX inhibitor, considerably reduced the LPS-induced HPA response in non-stressed rats and to a lesser extent diminished this response in repeatedly restrained or crowded rats. Neuronal NOS inhibitor, Nw-nitro-L-arginine decreased the LPS-induced HPA response, more potently in control than crowded rats. Aminoguanidine, an iNOS inhibitor, diminished the LPS-elicited ACTH response in crowded rats. These results indicate that prostaglandins and NO generated by neuronal and inducible NOS are involved in the LPS-induced HPA axis response under basal conditions and during its adaptation to chronic social stress circumstances.
INTRODUCTION: Traumatic experiences in childhood and maternal separation (MS) in rodents disrupts proper development of the brain including dopaminergic (DA) mesocorticolimbic pathways originating from ventral tegmental area (VTA). Importantly, early‑life stress predisposes for neuropsychiatric disorders and addiction in adulthood. Moreover, MS stress increases the number of VTA tyrosine hydroxylase (TH) immunoreactive DA neurons, raises baseline dopamine levels, and increases its release in response to acute stress in adult rats. However, neuronal mechanisms of these changes have not been fully explored. AIM(S): The current study aimed at determining the influence of MS on VTA DA cells electrophysiology and responsiveness to acute stress at the level of c-fos expression. METHOD(S): Female rats were submitted to MS during PND 2‑14, 3 h daily. In adulthood, some of the rats were subjected to restraint stress and subsequently perfused. The VTA region was cut, stained against TH and c-fos, and double stained neurons were counted. Remaining animals were sacrificed and brain slices containing VTA were prepared for electrophysiological patch‑clamp experiments. Recorded biocytin‑filled cells were stained and assessed as TH+ or TH‑. RESULTS: Our data show that exposure to early life stress leads to a significant reduction of the rheobase and an increased number of action potentials generated vs. injected current – indices of neuronal excitability. Importantly, it was altered in both TH+ and TH‑ VTA neurons. MS combined with restraint stress significantly increased the number of dorsal but not ventral VTA TH+/c‑fos+ cells. CONCLUSIONS: Observed changes in excitability of VTA DA neurons may constitute a neuronal mechanism of the reported elevated dopamine release after MS. Our data indicate that MS alters reactivity of dorsal but not ventral VTA cells to acute stress, which suggests a greater raise in stress-induced DA release in structures innervated by the dorsal VTA. FINANCIAL SUPPORT: Funding: NSC-Poland UMO- ‑2016/21/B/NZ4/00204.
Interleukin-1ß (IL-1ß) level is modulated during multiple stress reactions in both brain structures involved in hypothalamic-pituitary-adrenal (HPA) axis regulation and peripheral systems. Multiple distinct stressors induce different IL-1ß and HPA axis responses. The purpose of the present study was to determine if the effect of prior repeated restraint stress on IL-1ß levels in prefrontal cortex, hippocampus, hypothalamus and plasma may have an impact on alterations induced in HPA-axis responses. Experiments were performed on male Wistar rats which were exposed to 10 min restraint stress twice a day for 3 days. Twentyfour hour after the last stress period rats were injected i.p. with a single dose of IL-1ß, IL-1ß receptor antagonist or saline. After rapid decapitation, trunk blood was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen at -70°C. Total IL-1ß, ACTH and corticosterone (CORT) levels were determined in plasma using commercially available kits. Western blot analyses were performed on brain structures samples. Repeated restraint for 3 days alone substantially augmented the resting plasma levels of both IL-1ß, ACTH and CORT 24 h after the last restraint. Pretreatment with IL-1ß antagonist abolished the increase in ACTH and CORT responses to repeated stress. IL-1ß receptor antagonist also reduced the enhancement of plasma CORT level induced by 10 min stress. This suggests the selectivity of IL-1ß receptors in central and peripheral mechanisms modulating the stress-induced HPA axis responses. These results suggest that repeated stress increases IL-1ß production which activates ACTH and CORT secretion. Repeated stress also markedly enhanced IL-1ß level in brain structures involved in HPA axis regulation. The present results support the role of brain and peripheral IL-1ß in adaptation of HPA response during prolonged stress. Grant: POIG 01.01.02-12-004/09-00 financed by European Regional Development Fund.
Interleukin-1ß (IL-1ß) is crucial mediator of adaptative stress response of the hypothalamic-pituitary-adrenal (HPA) axis. The potential relationship between stress and brain IL-1ß has not been elucidated. Central and systemic administration of IL-1ß enhanced HPA axis activity. We examined the role of IL-1ß in ACTH and corticosterone (CORT) secretion and parallel alterations of IL-1ß in plasma and brain structures involved in HPA axis regulation. Experiments were performed on male Wistar rats. Non-stressed groups of rats were injected i.p. IL-1ß, IL-1ß receptor antagonist and saline. Stressed rats were exposed to 10 min restraint twice a day for 3 days. Twenty-four hour after the last stress period rats were treated like non-stressed. After decapitation trunk blood was collected and the brain prefrontal cortex, hippocampus and hypothalamus were excised and frozen at -70°C. Total CORT, ACTH and IL-1ß levels were determined using commercially available kits. Western blot analyses were performed on brain structures. Under basal conditions IL-1ß considerably increased plasma IL-1ß level, in a time dependent manner, more potently 1 h than 2 h following administration. By contrast plasma ACTH and CORT levels were more strongly enhanced at 2 h than 1 h after IL-1ß injection. This indicates that the most potent increase in plasma IL-1ß levels preceded a similar enhancement of ACTH and CORT secretion. IL-1ß receptor antagonist abolished the increase in ACTH and CORT responses to exogenous IL-1ß. Prior repeated stress increased IL-1ß production and sensitized ACTH and CORT responses to exogenous IL-1ß. Repeated stress also enhanced IL-1ß level in brain structures involved in HPA axis regulation and intensified this increase induced by exogenous IL-1ß. These results indicate the selective modulatory role of IL-1ß in HPA axis activation under basal and stress conditions. Financed by European Regional Development Fund, grant POIG 01.01.02-12-004/09-00.
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