Wyniki wyszukiwania - Biblioteka Nauki

1

Role of cytokines in pathogenesis of depression

100%

Kubera M.

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nr 3

2

The effect of a single transfusion of allogeneic or xenogeneic blood on skin allograft survival in mice

100%

Kubera M.

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nr 1-2

3

Effect of neonatal spleen and thymus implants on H-Y incompatible skin grafts

63%

Skowron-Cendrzak A. , Kubera M.

Folia Biologica

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1989

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tom 37

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nr 1-2

4

Prolongation of H-Y incompatible skin grafts in mice by neonatal spleen cells

51%

Kubera M. , Skowron-Cendrzak A. , Garlicki M.

Folia Biologica

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1989

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tom 37

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nr 3-4

5

Effect of co-treatment with fluoxetine and amantadine on the behavioral and immunological parameters of rats subjected to the forced swimming test

51%

Roguz Z. , Kubera M. , Basta-Kaim A.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

EN

Considerable attention has been paid to a possible role of immunological dysregulation in the pathogenesis of depression. It has been reported that combined administration of antidepressant drugs and the non-competitive NMDA receptor antagonist amantadine (AMA) reduces immobility time in the forced swimming test. Moreover, preliminary clinical data show that such a combination of drugs has benefi cial effects in treatment-resistant depressed patients. Since immune activation and a pro-infl ammatory response are clearly evident in treatment-resistant depression, the aim of the present study was to examine the effect of an antidepressant combination of FLU and AMA on immune parameters in rats subjected to the forced swimming test. The obtained results revealed synergistic antidepressant effects of combined administration of FLU (10 mg/kg) and AMA (10 mg/kg) – drugs otherwise ineffective when given separately in such doses. The antidepressant activity was accompanied with a reversal of the stress-induced increase in the proliferation of splenocytes in response to concanavalin A, and a signifi cant enhancement in the production of the negative immunoregulator interleukine-10. Moreover, the relative spleen weight in these rats was also reduced after joint administration of FLU with AMA in comparison with rats treated with the vehicle. In summary, the antidepressive effi cacy of a combination of FLU and AMA given in suboptimal doses may be related to their negative immune effects.

6

The influence of the age of donors and recipients on the regional graft-versus-hostreaction in mice

51%

Skowron-Cendrzak A. , Kubera M. , Bubak-Satora M. , Godowicz W.

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1991

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tom 39

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nr 3

7

Effects of estrone on quisqualate-induced toxicity in primary cultures of rat cortical neurons

51%

Kajta M. , Marszal M. , Kubera M. , Lason W.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 2

EN

Estrogens exert protective effects against neurotoxic changes induced by over-activation of ionotrophic glutamate receptors, whereas little is known about their interaction with changes mediated by metabotropic glutamate receptors. We evaluated effects of estrone on quisqualate (QA)-induced toxicity in neuronal cell cultures on 7 and 12 day in vitro (DIV). Twenty four hour exposure to QA (150 µM and 300 µM) significantly decreased cell survival in 7 day old cultures, but the 12 day old cultures were more resistant to its toxicity. DNQX (10 µM), an AMPA/kainate receptor antagonist, partly attenuated the toxic effects of QA, whereas LY 367 385 (100 µM), a selective mGluR1alpha antagonist, completely reversed the above effect. QA did not activate, but suppressed spontaneous caspase-3-like activity. Estrone (100 nM and 500 nM) attenuated QA-mediated neurotoxic effects independently of estrogen receptors, as indicated with ICI 182, 780 and without affecting the caspase-3-like activity. At early stage of development in vitro (7 DIV) toxic effects of QA were more profound and mediated mainly by metabotropic glutamate receptors of group I, whereas later (12 DIV) they were mediated mostly by ionotropic AMPA/kainate receptors. The toxic effects of QA were partly accompanied by anti-apoptotic action against spontaneous caspase-3-like activity, possibly due to modulation of neuronal plasticity.

8

Down-regulating effect on cellular immunity of the NSF17 factor produced by murine neonatal spleen cells fused with BW 5147 thymona cells

45%

Bubak-Satora M. , Machala O. , Kubera M. , Mazur-Kolecka B. , Skowron-Cendrzak A.

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tom 40

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nr 1-2

9

Induction of indomethacin-sensitive suppressor cells by xenogeneic blood transfusion in mice

38%

Kubera M. , Holan V. , Skowron-Cendrzak A. , Bubak-Satora M. , Stedra J. , Mazur-kolecka B.

Folia Biologica

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1989

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tom 37

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nr 1-2

10

The effect of antidepressant drugs on immunoendocrine changes in animal models of depression

38%

Budziszewska B. , Kubera M. , Szymanska M. , Basta-Kaim A. , Grygier B. , Lason W.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

EN

Exacerbated glucocorticoids and cytokines action are essential factor in the pathogenesis of depression, and the effects of antidepressant drugs on these parameters are poorly recognized.We investigated the effect of antidepressant drugs on the HPA axis activity in prenatally stressed S-D rats and on cell-mediated immunity in Wistar rats and C57BL/6 mice subjected to chronic mild stress (CMS) model of depression. The activity of HPA axis was estimated by measuring the level of glucocorticoid receptors (GR) and activity of some kinases which are known to infl uence GR action. Adult rats subjected to prenatal stress displayed prolonged immobility in the Porsolt test and in open-fi eld test, elevated corticosterone level, increased GR level in the hippocampus but not in frontal cortex. They also showed decreased FKBP51 in the frontal cortex, but not in hippocampus, decreased the active, phosphorylated form of the JNK1 and 2 kinase in the hippocampus and the active form of p38-MAPK in the frontal cortex. Chronic imipramine, fl uoxetine, mirtazapine or tianeptine administration normalized most of these parameters. In CMS model of depression anti-anhedonic effect of imipramine was accompanied by decreased proliferative activity of splenocytes and their ability to produce pro-infl ammatory cytokines in rats. In desipramine treated mice subjected to CMS increased ability of T cells to produce negative immunoregulator IL-10 and decreased the cytotoxic activity of NK cells were observed.

11

Characteristics of the neonatal spleen cell subpopulation in mice which suppresses lymphocyte prolifer ative response to mitogen stimulation

38%

Mazur-Kolecka B. , Kubera M. , Stedra J. , Holan V. , Skowron-Cendrzak A. , Burak-Satora M.

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nr 1-2

12

Inhibitory effect of antipsychotic drugs on the CON A- and LPS- induced proliferative activity of mouse splenocytes: a possible mechanism of action

38%

Basta-Kaim A. , Budziszewska B. , Jagla G. , Nowak W. , Kubera M. , Lason W.

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2006

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tom 57

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nr 2

EN

Antipsychotic drugs are widely used to alleviate a number of psychic disorders and have been found to modulate some immune parameters, but the molecular mechanism of their action on the proliferative activity has been poorly recognized. In the present study, we investigated effects of various antipsychotics on the proliferative activity of lymphocytes stimulated by concanavalin A (Con A) and lipopolysaccharide (LPS). Chlorpromazine (3x10-6 - 10-4M) showed the most potent effect in inhibiting 3H-thymidine incorporation into C57BL/6 mouse spleen cells stimulated by Con A and LPS. Treatment of the cells with thioridazine (10-5 - 10-4M), promazine (10-5 - 10-4M), haloperidol (10-5 - 10-4M), risperidone (10-5 - 10-4M), raclopride (3x10-5 - 10-4M), remoxipride (3x10-5 - 10-4M) and clozapine ( 3x10-5 - 10-4M), but not with sulpiride (10-7 - 10-4M), suppressed proliferative activity of splenocytes after Con A stimulation. On the other hand, LPS-induced proliferation of splenocytes was inhibited by clozapine, promazine, thioridazine and haloperidol, but not by risperidone, remoxipride, sulpiride and raclopride. In the next part of the study, the influence of some kinase modulators on chlorpromazine- and clozapine-evoked inhibition of the proliferative activity of splenocytes was determined. Wortmannin, a selective phosphatidylinositol 3-kinase (PI3-K) inhibitor, blocked chlorpromazine and clozapine inhibitory effect on the mitogen-stimulated splenocyte proliferation. The involvement of PI 3-K /protein kinase B (PKB, Akt) pathway was confirmed by the results of the Western blot study, which showed that both drugs increased the level of active phospho-Ser-473 Akt, without changing the total Akt level, and decreased the level of active, nonphosphorylated glycogen synthase kinase-3 (GSK-3ß). Additionally, we have found that chlorpromazine action was also attenuated by a selective p-38-MAPK inhibitor, while clozapine effect was suppressed by a protein kinase C (PKC) activator. The obtained results indicated that atypical antipsychotic drugs markedly inhibited the proliferative activity of splenocytes only after ConA stimulation. Inhibition of the proliferative capability of splenocytes by chlorpromazine and clozapine resulted mainly from the activation of PI3-K/Akt pathway.

13

Effects of combined treatment with imipramine and metyrapone on the immobility time, the activity of hypothalamo-pituitary-adrenocortical axis and immunological parameters in the forced swimming test in the rat

38%

Rogoz Z. , Budziszewska B. , Kubera M. , Basta-Kaim A. , Jaworska-Feil L. , Skuza G. , Lason W.

Journal of Physiology and Pharmacology

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2005

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tom 56

|

nr 1

EN

Major depression is frequently associated with the hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. The aim of the present study was to examine the effect of joint administration of metyrapone (50 mg/kg) and imipramine (5 and/or 10 mg/kg) on immobility time, plasma corticosterone concentration, the weight of spleens and thymuses and the proliferative activity of splenocytes in rats subjected to the forced swimming test - an animal model of depression. Metyrapone alone (50 mg/kg) reduced the immobility time of rats in the forced swimming test and decreased plasma corticosterone level, but did not change immunological parameters. Joint administration of metyrapone and imipramine (5 and 10 mg/kg) produced a more pronounced antidepressant-like effect than either of the drugs given alone. The forced swimming procedure significantly increased the proliferative activity of splenocytes, that parameter being reduced only by co-administration of metyrapone and imipramine. Joint administration of metyrapone and imipramine inhibited to a similar extend the corticosterone level as did treatment with metyrapone alone (about twofold); however, the plasma corticosterone level in animals treated with metyrapone and the higher dose of imipramine did not differ from the concentration of this steroid in control, not-stressed rats. The obtained results indicate that metyrapone potentiates the antidepressant-like activity of imipramine and exerts a beneficial effect on the stress-induced increase in plasma corticosterone concentration and the proliferative activity of splenocytes. These finding suggest that a combination of metyrapone and an antidepressant drug may be useful for the treatment drug-resistant depression and/or depression associated with a high cortisol level.

14

Immunomodulatory effect of antidepressant drugs in animal models of depression

32%

Kubera M. , Basta-Kaim A. , Budziszewska B. , Jaworska-Feil E. , Roman A. , Leskiewicz M. , Telich M. , Korzeniak B. , Lason W.

Acta Neurobiologiae Experimentalis

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2005

|

tom 65

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nr 3

15

The decrease in JNK- and p38-MAP kinase activity is accompanied by the enhancement of PP2A phosphatase level in the brain of prenatally stressed rats

32%

Budziszewska B. , Szymanska M. , Leskiewicz M. , Basta-Kaim A. , Jaworska-Feil L. , Kubera M. , Jantas D. , Lason W.

Journal of Physiology and Pharmacology

|

2010

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tom 61

|

nr 2

EN

Our previous study suggests that in prenatal stress model of depression glucocorticoid receptor (GR) function in adult rats is enhanced. However, the long-term consequences of stress, a causal factor in depression, on intracellular elements involved into the regulation of GR function is poorly examined. Mitogen-activated protein kinases (MAPKs), activity of which is disturbed in depression, are important regulators of GR action, so they can mediate the effect of stress on GR function. Therefore, the aim of the present study was to investigate the levels of active phosphorylated forms of extracellular signal-regulated kinases (ERK), Jun N-terminal kinases (JNK) and the p38 kinase in the hippocampus and frontal cortex in rats subjected to prenatal stress. The concentration of MAP kinase phosphatase (MKP-1, MKP-2) and protein phosphatase-2A (PP2A), which dephosphorylate all forms of MAP kinases, were also determined. During verification of the applied model of depression, we found that prenatally stressed rats displayed high level of immobility in the Porsolt test and that the administration of imipramine, fluoxetine, mirtazapine and tianeptine for 21 days normalized this parameter. Western blot study revealed that rats subjected to prenatal stress had decreased levels of p-JNK1 and p-JNK2 in the hippocampus and p-p38 in the frontal cortex, but the concentrations of p-ERK1 and p-ERK2 were not changed. Chronic treatment with imipramine inhibited the stress-induced decrease in p-JNK1/2, while imipramine, fluoxetine and mirtazapine blocked changes in p-p38. PP2A phosphatase level was higher in the hippocampus and frontal cortex in prenatally stressed animals than in control rats. Chronic treatment with antidepressant drugs attenuated the stress-induced increase in the level of this phosphatase, but had no effect on its concentration in control animals. There was no significant difference in MKP-1 and in MKP-2 levels in both brain structures between control and prenatally stressed rats. The obtained results showed that prenatal stress decreased the levels of active form of JNK and p38, but enhanced PP2A phosphatase expression and most of these changes were reversed by antidepressant drugs. Since p-JNK and p-p38 are known to inhibit GR function their lowered levels may enhance glucocorticoid action. Furthermore, the increased PP2A concentration may intensify GR action not only by inhibition of JNK and p38 phosphorylation, but also by a direct influence on the process of GR translocation.

16

The effect of amphetamine sensitization on mouse immunoreactivity

32%

Kubera M. , Filip M. , Basta-Kaim A. , Nowak E. , Budziszewska B. , Tetich M. , Holan V. , Korzeniak B. , Przegalinski E.

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nr 2

EN

Recent studies indicate a role of the immune system in the behavioral effects of amphetamine in rodents. In the present study we attempted to find a connection between the behavioral changes induced by repeated, intermittent administration of amphetamine and some immunological consequences of sensitization to amphetamine in mice. Male Albino Swiss mice were treated repeatedly (for 5 days) with amphetamine (1 mg/kg, i.p.). On day 9, they received a challenge dose of amphetamine (1 mg/kg). Acute administration of amphetamine increased their locomotor activity by ca. 40%. In animals treated repeatedly with amphetamine, the challenge dose of the psychostimulant induced behavioral sensitization, i.e. the higher locomotor activation as compared with that after its first administration to mice. Immune functions were evaluated by the ability of splenocytes to proliferate and to produce cytokines such as interferongamma(IFN-gamma ), interleukin (IL)-4 and IL-10. Acute amphetamine administration significantly decreased, by ca. 30% and 25%, the proliferation of splenocytes in response to an optimal and a suboptimal dose of concanavalin A (Con A), respectively, and increased their ability to produce IL-4. Chronic intermittent treatment with amphetamine significantly decreased, by ca. 65% and 50%, the proliferative response of T cells to an optimal and a suboptimal dose of Con A, respectively, and diminished by 20% the metabolic activity of splenocytes. The above data showed that both acute and chronic amphetamine administration diminished some aspects of the cell-mediated immunity; nevertheless, immunosuppression was particularly evident in amphetamine-sensitized mice. Our findings seem to indicate possible importance of monitoring and correcting immune changes in the therapy of amphetamine addiction.