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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.
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