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Chronic stress, by initiating changes in the hypothalamic-pituitaryadrenal (HPA) axis and the immune system, acts as a trigger for neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) is highly involved in regulation of HPA activity. The aim of the study was to investigate the influence of acute immunostimulation on the of BDNF in the hypothalamus and pituitary of rats subjected to chronic stress. Female Sprague-Dawley rats were subjected to 4-week stress, including phases of isolation and crowding, in an unpredictable manner. On the last day of the experiment rats being at the estrus phase were injected ip. with LPS (1 mg/kg/2 ml) or saline. Six hours later the brain structures were rapidly isolated. QRT-PCR experiments were performed using TaqMan Gene Expression Assays. The BDNF concentration was measured with a conventional ELISA assay. In the hypothalamus and pituitary of LPS-treated stressed rats BDNF mRNA expression was decreased in comparison to saline-treated stressed group. We concluded that chronic stress and inflammation have synergistic deleterious influence on BDNF in the studied structures.
It is widely accepted that chronic stress leads to the development of, and is associated with, mood disorders. Exposure to stress may intensify consequences of neuroinflammation which is considered as a crucial mechanism leading to CNS injury involving the neuroanatomical alterations in hippocampus – structure play a significant role for mechanism of action of antidepressants. Chronic treatment with some antidepressants up-regulate expression of BDNF which is the key neurotrophic factor promoting cell survival and neuroplasticity. The study was carried out to investigate the influence of desipramine, fluoxetine or tianeptine given chronically on the lipopolysaccharide (LPS) effect on the expression and the level of BDNF in hippocampus of female rats subjected to chronic stress. In the hippocampus of LPS-treated rats subjected to chronic stress, BDNF mRNA and protein levels were reduced, in comparison to the stress-group. The LPS effect was protected by treatment with studied antidepressants. The protection of BDNF against the deleterous synergistic effect induced by inflammation and chronic stress may have significance for therapeutic effects of long-term treatment with antidepressants.
It is suggested that glial activation play an important role in the pathogenesis of psychiatric and neurodegenerative diseases. Activated glial cells secrete various cytokines. Anti-infl ammatory effect of imipramine, moclobemide, fl uoxetine was investigated using 13–14 day primary rat mixed glial cultures prepared from cerebral hemispheres of one-day old newborn Wistar rats. LPSstimulated levels of TNF-α, IL-1β, IL-10 were measured with ELISA kits in culture medium. Antidepressants were used at concentrations from 108 to 100 μM. mRNA for cytokines was evaluated by RT-QPCR. Moclobemide, fl uoxetine (108 to 10 μM) and imipramine (106 to 100 μM) reduced TNF-α release. IL-1β concentration was diminished by moclobemide, imipramine (106 to 100 μM) and fl uoxetine (10-6 to 10 μM) but level of IL-10 was not changed signifi cantly after drug administration. The levels of TNF-α or IL-1β mRNA were reduced by the studied drugs (10 μM), whereas IL-10 mRNA level was only attenuated. Our results support observation that antidepressants have anti-infl ammatory effects in CNS because they affected the balance between proand antiinfl ammatory cytokines (TNF-α, IL-1β/IL-10) in mixed glial culture. This work was supported by Grant N 401 130 31/2871 from the Ministry of Science and Higher Education.
Protective potential of immunosuppressants has been reported in many experimental models of ischemia both in vivo and in vitro suggesting novel therapeutic application of these drugs. On account of fact that high mobility group box 1 (HMGB1) protein has recently been reported to be involved to ischemic brain injury, the purpose of the present study was to determine whether treatment with immunosuppressants could decrease HMGB1 expression and release in astrocytes exposed to ischemia-simulating conditions (combined oxygen glucose deprivation, OGD). We also studied the infl uence of these drugs on expression of NFκB, inducibleNO synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, we investigated whether the immunosuppressants could attenuate of necrosis in astrocyte cultures exposed to OGD. Cells were treated with cyclosporine A, FK506 and rapamycin (all drugs at concentrations of 0.1, 1 and 10 mM). Our study has provided evidence that immunosuppressants decrease the expression and release of HMGB1 in ischemic astrocytes. The present results provide further information about the cytoprotective mechanisms of immunosuppressants towards ischemic astrocytes, in relation to the pathophysiology of ischemic brain injury. It appears that the immunosuppressants stimulated protective effects could be mediated in part by suppression of HMGB1 expression and release in astrocytes, what leads to attenuation of ischemia-induced necrosis and neuroinfl ammation.
Introduction: In the autumn of 2009 the authors participated in a humanitarian operation in Western Ukraine by undertaking an epidemiological investigation of an influenza-like-illness (ILI) in the L’viv Oblast region. Mobile biological survey teams took samples from civilian patients with severe acute respiratory distress syndrome, rapid transportation of the samples, and their molecular analysis in Poland to provide accurate results. Objective: The aim of the study was the molecular and epidemiological analysis of the biological samples collected. Material and Methods: Real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR), multiplex PCR techniques, traditional Sanger Sequencing and classical viral culture methods were used. Results: Among the 124 influenza-like illness cases, ~50% (58) were positive for influenza A virus in WHO-CDC molecular assay, including subtyping. The specimens were further analyzed to confirm results and determine the genetic sequence. Phylogenetically, the nucleotide similarity of both the Ukraine specimens and reference A/California/7/2009 (pH1N1) was 99.2–99.3%. Oseltamivir resistance was not registered. HA1 region characterization showed an overall protein identity of 98.5–99.4%. Conclusions: An unexpected high contribution of influenza A was confirmed among ILI patients, as well as a very limited number of other detected viruses, indicate that the 2009 epidemic in western Ukraine was strongly related to novel influenza A/H1N1. The importance of swift sharing of information and reference laboratories networking in surveillance, as well as serving governments and international agencies in pursuing adequate actions, should be stressed.
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