Wyniki wyszukiwania

1

Ifenprodil and NMDA ligands

100%

Wosko S., Szopa A., Serefko A., Poleszak E.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Depression is one of the most common affective disorders. According to the World Health Organization (WHO), it is currently the fourth major global health problem (Kessler et al. 2003). The growing number of people suffering from depression has motivated the scientists to search for new antidepressant drugs. Since numerous studies revealed that NMDA receptor may be involved in the mechanism of action of the antidepressant agents, modulation of the NMDA receptor function by different ligands has been taken into consideration. There are some promising results demonstrating the antidepressant activity of the antagonists binding to the polyamine site of the NMDA receptor complex. Ifenprodil belongs to a family of the selective, atypical non-competitive antagonists of the NMDA receptors. It acts via inhibition of the polyamine binding site of the NR2B subunit (Williams 1993). An antidepressantlike effect of ifenprodil was observed in several behavioral studies, for example in the forced swimming test (Carter et al. 1990, Williams 1993, Layer et al. 1995, Scolnik 1999, Paoletti and Neyton 2007). It was shown that its antidepressant-like activity is increased by other antidepressant drugs (imipramine and fluoxetine). The aim of our work was to evaluate the antidepressant activity of the joint administration of ifenprodil and NMDA ligands in the mouse forced swimming test (FST). The experiments were carried out on male Albino Swiss mice. In order to avoid the risk of obtaining the false positive/negative effects in the FST test caused by a possible influence of the tested substances on the locomotor activity, the spontaneous locomotor activity was measured. The obtained results demonstrated that ifenprodil at the dose of 10 mg/ kg enhances the antidepressant-like effect of the following NMDA receptor ligands: a competitive NMDA receptor antagonist – CGP 37849 (0.312 mg/kg), an antagonist at glycine site – L-701,324 (1 mg/kg) and a non-competitive antagonist at phencyclidyne – MK801 (0.05 mg/kg). However, it did not potentiate the antidepressant activity of the inorganic modulators of the NMDA receptor complex, such as Zn2+ (2.5 mg/kg) and Mg2+ (10 mg/kg). Treatment with the tested agents did not influence the locomotor activity. In conclusion, our findings indicated that antidepressant-like activity of ifenprodil is connected with serotoninergic and glutamatergic system.

2

Increased gene expression of selected vesicular and glial glutamate transporters in the frontal cortex in rats exposed to voluntary wheel running

86%

Graban J., Hlavacova N., Jezova D.

Journal of Physiology and Pharmacology

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2017

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tom 68

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nr 5

3

NMDA glutamate receptor antagonism and the ventilatory response to hypoxia in the anesthetized rat

72%

Tarakanov I., Dymecka A., Pokorski M.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 3

139-147

This study seeks to discern the influence of the NMDA glutamate-mediated pathway in the early stimulatory and late depressant phases of the hypoxic ventilatory response. We addressed this issue by recording ventilation before and after intravenous administration of the NMDA receptor antagonist MK-801 during acute, steady-state hypoxic challenges in the anesthetized, spontaneously breathing rats. Minute ventilation and its volume and frequency components were calculated and compared at the peak and nadir of the hypoxic response. We found that NMDA receptor antagonism appreciably affected both ventilatory phases of hypoxia. The early stimulation of ventilation was attenuated and the late depression was accentuated. The latter consisted of abolishment of the characteristic sustenance of hypoxic ventilation above the baseline level in the depressant phase, so that ventilation declined down to the baseline after NMDA receptor blockade. The inability to uphold ventilation in the depressant phase suggests that the NMDA glutamate-mediated pathway is operative in shaping the late hypoxic ventilatory response. The role of the glutamatergic pathway may thus be extended beyond the hitherto recognized early ventilatory stimulation of hypoxia.

4

Hyperhomocysteinemia as a risk factor for the neuronal system disorders

72%

Petras M., Tatarkova Z., Kovalska M., Mokra D., Dobrota D., Lehotsky J., Drgova A.

Journal of Physiology and Pharmacology

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2014

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tom 65

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nr 1

5

Intermingled modulatory and neurotoxic effects of thimerosal and mercuric ions on electrophysiological responses to GABA and NMDA in hippocampal neurons

72%

Wyrembek P., Szczuraszek K., Majewska M. D., Mozrzymas J. W.

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 6

6

Activation of NMDA-sensitive glutamate receptors triggers release of taurine in rabbit hippocampus during ischemia

72%

Puka M., Salinska E., Pluta R., Lazarewicz J. W.

Bulletin of the Polish Academy of Sciences. Biological Sciences

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1990

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tom 38

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nr 1-12

7

Expression of N-methyl-D-aspartate (R)(GluN2B) - subunits in the brain structures of rats selected for low and high anxiety

58%

Lehner M., Wislowska-Stanek A., Skorzewska A., Maciejak P., Szyndler J., Turzynska D., Sobolewska A., Krzascik P., Plaznik A.

Journal of Physiology and Pharmacology

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2011

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tom 62

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nr 4

8

Is the NMDA receptor involved in neurotoxicity of pvp-coated silver nanoparticles? Study on primary cultures of cerebellar granule cells

58%

Zieminska E., Stafiej A., Struzynska L.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Silver nanoparticles (NAg) possess antibacterial properties thus are widely used in many applications in medicine, life sciences and biotechnology. Nanoparticles can be found in vertebrate brain, but little is known about their neurotoxicity. The aim of this study was to investigate how NAg can contribute to neuronal cell death. In the study primary cultures of rat cerebellar granule cells (CGC) were used. We tested hypothesis concerning the role of glutamatergic NMDA receptors in NAg-evoked neurotoxicity. In our study changes in intracellular calcium (Ca2+) homeostasis, uptake of 45Ca2+, reactive oxygen species (ROS) production, mitochondrial membrane potential and cells viability were investigated. We used commercially available 0.2% polyvinylpyrrolidone (PVP)-coated NAg <100 nm. To avoid sedimentation and agglomeration, before application to the CGC culture, NAg were sonicated with fetal calf serum. NAg were applied in concentration 2.5–75 µg/ml for 10, 30 min or 24 h, depending on experiment. As a pharmacological tool 0.5 µM MK801, a noncompetitive inhibitor of NMDA receptor, was used. After 10 min incubation in the presence of 25–75 µg/ ml NAg dose dependent increase of 45Ca2+ concentration was observed in neurons. This increase was comparable to that evoked by 100 µM glutamate and was completely abolished by MK801. Using fluorescent intracellular calcium indicator fluo3 we observed increase in intracellular calcium level by 200% compared to control, which was partially diminished by MK801. ROS production was measured using fluorescent dye DCF. After 30 min incubation with 75 µg/ml NAg the increase by about 35% over control level was observed and application of MK801 reduced it significantly. Changes in mitochondrial membrane potential were determined using rhodamine (R123). We observed significant decrease in mitochondrial potential during 30 min incubation with different concentrations of NAg and also in this case administration of MK801 was protective. Cells viability was assessed after 24 h incubation with NAg µg/ml alone or together with MK801. Application of MK801 increased neuronal survival from 50% up to 80%. Our results show that excitotoxicity via activation of NMDA receptor, followed by calcium imbalance, destabilization of mitochondrial function and ROS production, seems to be important mechanism involved in neurotoxicity evoked by NAg in cultured neurons. Supported by grant NN401619938.

Ograniczanie wyników

Ifenprodil and NMDA ligands

Increased gene expression of selected vesicular and glial glutamate transporters in the frontal cortex in rats exposed to voluntary wheel running

NMDA glutamate receptor antagonism and the ventilatory response to hypoxia in the anesthetized rat

Hyperhomocysteinemia as a risk factor for the neuronal system disorders

Intermingled modulatory and neurotoxic effects of thimerosal and mercuric ions on electrophysiological responses to GABA and NMDA in hippocampal neurons

Activation of NMDA-sensitive glutamate receptors triggers release of taurine in rabbit hippocampus during ischemia

Expression of N-methyl-D-aspartate (R)(GluN2B) - subunits in the brain structures of rats selected for low and high anxiety

Is the NMDA receptor involved in neurotoxicity of pvp-coated silver nanoparticles? Study on primary cultures of cerebellar granule cells