Wyniki wyszukiwania

1

Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease

100%

Hannan A. J.

Acta Biochimica Polonica

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2004

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tom 51

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nr 2

Huntington's disease (HD) is an autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. HD is caused by a trinucleotide (CAG) repeat mutation, encoding an expanded polyglutamine tract in the huntingtin protein. At least eight other neurodegenerative diseases are caused by CAG/glutamine repeat expansions in different genes. Recent evidence suggests that environmental factors can modify the onset and progression of Huntington's disease and possibly other neurodegenerative disorders. This review outlines possible molecular and cellular mechanisms mediating the polyglutamine-induced toxic 'gain of function' and associated gene-environment interactions in HD. Key aspects of pathogenesis shared with other neurodegenerative diseases may include abnormal protein-protein interactions, selective disruption of gene expression and 'pathological plasticity' of synapses in specific brain regions. Recent discoveries regarding molecular mechanisms of pathogenesis are guiding the development of new therapeutic approaches. Knowledge of gene-environment interactions, for example, could lead to development of ‘enviromimetics’ which mimic the beneficial effects of specific environmental stimuli. The effects of environmental enrichment on brain and behaviour will also be discussed, together with the general implications for neuroscience research involving animal models.

2

Synaptic plasticity of local connections in rat motor cortex

84%

Hess G.

Acta Neurobiologiae Experimentalis

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2004

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tom 64

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nr 2

3

Long-term potentiation and long-term depression of horizontal connections in rat motor cortex

84%

Hess G., Donoghue J. P.

Acta Neurobiologiae Experimentalis

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1996

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tom 56

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nr 1

4

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

67%

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

5

The 5-HT7 receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex

67%

Tokarski K., Bobula B., Kusek M., Hess G.

Journal of Physiology and Pharmacology

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2011

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tom 62

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nr 6

6

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

67%

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

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 2

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.

7

Synaptogenesis and structure of the autonomic ganglia

67%

Majewski M.

Folia Morphologica. Supplement

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1999

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tom 58

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nr 2

8

Leon L. Voronin [1938-2004] Neuroscientist with the soul of a poet

67%

Bregestovski P., Turlejski K.

Acta Neurobiologiae Experimentalis

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2005

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tom 65

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nr 1

9

Protein kinase C in the barrel cortex

67%

Nowicka D.

Acta Neurobiologiae Experimentalis

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2000

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tom 60

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nr 4

10

L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol stimulates ganglioside biosynthesis, neurite outgrowth and synapse formation in cultured cortical neurons, and ameliorates memory deficits in ischemic rats

67%

Inokuchi J., Kuroda Y., Kosaka S., Fujiwara M.

Acta Biochimica Polonica

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1998

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tom 45

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nr 2

To address the role of brain gangliosides in synaptic plasticity, the synthetic ceramide analog, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) was used to manipulate the biosynthesis of gangliosides in cultured cortical neurons. Spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons, which represents synapse formation, was suppressed by the depletion of endogenous gangliosides by D-threo-PDMP, an inhibitor of glucosylceramide synthase. The decreased functional synapse formation was normalized by supplementation of GQ1b but not by the other gangliosides, suggesting that de novo synthesis of ganglioside GQ1b is essential for the synaptic activity (Mizutani A. et al., Biochem. Biophys. Res. Commun. 222, 494-498, 1996). On the other hand, the enantiomer of the inhibitor, L-threo-PDMP, could elevate cellular levels of glycosphingolipids including gangliosides. This paper presents our recent findings on the neurotrophic actions of L-threo-PDMP in vitro and in vivo. We found that L-PDMP could up-regulate neurite outgrowth, functional synapse formation and ganglioside biosynthesis through activating GM3, GD3 and GQ1b synthases. Simultaneously, the activity of p42 mitogen-activated protein kinase was also facilitated by L-PDMP. To evaluate the efficacy of this drug on long term memory, rats were trained for 2 weeks using an 8-arm radial maze task, and then forebrain ischemia was induced by 4-vessel occlusion (for 10 min × 2 with a 60 min interval). Repeated treatment of L-threo-PDMP (40 mg/kg, i.p. for 6 days, twice a day) starting 24 h after the ischemia, improved the deficit of the well-learned spatial memory, demonstrating the potential therapeutic use of the ceramide analog for treatment of neurodegenerative disorders.

11

Presynaptic phosphoprotein B-50-GAP-43 in neuronal and synaptic plasticity

67%

Biewenga J. G., Schrama L. H., Gispen W. H.

Acta Biochimica Polonica

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1996

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tom 43

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nr 2

B-50/GAP-43 is a growth-associated phosphoprotein enriched in growth cones and in the presynaptic terminal. The expression of the protein is restricted to the nervous system and is highest in the first week after birth. In adult brain, B-50 is enriched in areas with high plasticity. The regulation of expression of the B-50 gene occurs both at the transcriptional and post-transcriptional level by unknown mechanisms. The gene contains 2 regions displaying promoter activity, the most 3' of which (P2) is the active one in vivo. Expression of B-50 in non-neuronal cells results in filopodial extensions whereas antibodies or antisense oligo's to B-50 prevent neurite outgrowth. The protein is important for neuronal pathfinding. Several post-translational modifications have been described, ADP-ribosylation and palmitoylation in the membrane binding domain, phosphorylation by PKC, casein kinase II and phosphorylase kinase, and dephosphorylation by several phosphatases, among which is calcineurin. Interactions of B-50 have been described with calmodulin, PIP kinase, F-actin, and phospholipids. Recent studies indicate that the phosphorylation state and amount of calmodulin bound to B-50 regulate the rate of transmitter release. Induction of long-term potentiation by high frequency stimulation of hippocampal slices results in an increased state of B-50 phosphorylation. This will increase the amount of free calmodulin in the presynaptic terminal and increase the amount of transmitter released. Although B-50 is involved in seemingly unrelated forms of neuronal plasticity, neurite outgrowth and transmitter release, our unifying hypothesis is that the protein plays an (unknown) essential, modulatory role in membrane expansion.

12

MAPK regulation of gene expression in the central nervous system

51%

Adams J. P., Roberson E. D., English J. D., Selcher J. C., Sweatt J. D.

Acta Neurobiologiae Experimentalis

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2000

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tom 60

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nr 3

13

Involvement of membraneous sialoglycosphingolipids [gangliosides] in the process of transmission and storage of information in the brain of vertebrates

51%

Rahmann H.

Biophysics of Membrane Transport

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1994

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tom 12

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nr 2

Ograniczanie wyników

Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease

Synaptic plasticity of local connections in rat motor cortex

Long-term potentiation and long-term depression of horizontal connections in rat motor cortex

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

The 5-HT7 receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex

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

Synaptogenesis and structure of the autonomic ganglia

Leon L. Voronin [1938-2004] Neuroscientist with the soul of a poet

Protein kinase C in the barrel cortex

L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol stimulates ganglioside biosynthesis, neurite outgrowth and synapse formation in cultured cortical neurons, and ameliorates memory deficits in ischemic rats

Presynaptic phosphoprotein B-50-GAP-43 in neuronal and synaptic plasticity

MAPK regulation of gene expression in the central nervous system

Involvement of membraneous sialoglycosphingolipids [gangliosides] in the process of transmission and storage of information in the brain of vertebrates