Wyniki wyszukiwania - Biblioteka Nauki

1

Brain injury: prolonged induction of transcription factors

100%

Pennypacker K. R. , Kassed K. C. A. , Kassed C. A. , Eidizadeh E. S. , Eidizadeh S. , O. C. J. P. , O?Callaghan J. P. , O?Callaghan J. P.

Acta Neurobiologiae Experimentalis

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2000

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tom 60

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nr 4

515-528

EN

A specific temporal order of events at the cellular and molecular level occurs in response to injury to the brain. Injury-compromised neurons degenerate while surviving neurons undergo neuritogenesis and synaptogenesis to establish neuronal connectivity destroyed in the injury. Several genes, such as those coding cytoskeletal proteins and growth factors, have been shown to be regulated by AP-1 and NF-kB transcription factors, two of the most studied DNA binding regulatory proteins. Our laboratory has discovered that Fos-related antigen-2 from AP-1 transcription factor family and NF-kB p65 and p50 subunits are induced long-term (days to months) in the brain after neurotoxic, excitotoxic or ischemic insult. Fos-related antigen-2 is induced in neurons in several models of injury and its elevated expression lasts days to months, corresponding to the severity. The time-course of FRA-2 induction is abbreviated with less severe insult (terminal damage) relative to the cell death, but the induction occurs during the period of regeneration and repair in both models. NF-kB p65 is basally expressed in hippocampal and cortical neurons, but is elevated in reactive astrocytes in hippocampus and entorhinal cortex starting at two days and lasting at least two weeks after kainate treatment. Neurons of the hippocampus surviving ischemic or neurotoxic injury increase expression of NF-kB p50 for at least a week after injury, suggesting a function for p50 in neuronal survival and/or repair. The extended expression of these transcription factors implies a role in the activation of genes related to repair and regeneration, such as growth factors and synaptic proteins, after injury to the CNS.

2

Possible consequences of disruption of neuromuscular contacts in early development for motoneurone survival

81%

Greensmith L. , Sieradzan K. , Vrbova G.

Acta Neurobiologiae Experimentalis

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1993

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tom 53

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nr 1

319-324

EN

Motoneurones are known to die (1) during embryonic development (naturally occurring cell death), (2) early in postnal development after axonal injury, and (3) as a consequence of disease such as SMA. Interactions with the target emerges as an important factor for survival of developing montoneurones. The evidence for the target dependence od of developing motoneurones will be presented and the mechanisms by which the muscle may regulate motoneurone survival discussed. Results that argue for the following proposal will be given: with maturation of the CNS motor activity in all mammals increases as do the functional demands on the motoneurones. The target muscle's role is to induce changes in the motoneurone to make it competent to respond to increased amounts of glutamate from excitatory inputs and thus allow it to carry out the tasks associated with its increased activity. A failure of the muscle to induce these changes in the motonerone's phenotype in time may lead to motoneurone death. In addition new approaches that could (1) improve motoneurone survival, and (2) use embryonic grafts to replace the lost cells will be discussed.

3

Gene expression in neuronal apoptosis-looking far a therapeutic window

81%

Figiel I. , Filipkowski R. K. , Hetman M. K. B. , Kaczmarek L.

Biotechnologia

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1996

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nr 4

132-140

EN

Wxititixicity - cell loss occurring after an excessive stimulation with excitatory amino acid - has been suggested to underlie major neurodegenerative disorders.Recent studies imply that this phenomenon may have an apoptotic character, i.e.., it may be an active process.In our studies, revived herein, we confirmed and extended this view by demonstratijng a gene expression component in the processes of neuronal cell loss in three different experimental models: i. kinate administration, II, high-dose MK-801 treatment, iii.glutamate stimulation of dentate gyrus neurons cultured in vitro.In conclusion we suggest that these data, as well as tha results of a number of other studies offer a hope that there ia a therapeutic window for the treatment of a neurodegenerative diseases, both in respect to time between the insult and cell death, and through possible common mechanisms to be targeted by future therapies.One can even speculate that such therapies might aim at transcription factors, e.g. AP-1 of a specific composition and/or executor hydrolytic enzymes, e.g., cathepsin D.

4

How does trimethyltin affect the brain:facts and hypotheses

71%

Koczyk D.

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1996

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tom 56

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nr 2

587-596

EN

Trimethyltin, an organic compound of tin, is a potent neurotoxicant of mechanism of action yet to be uncovered.The neuropathological findings that causes selective hippocampal damage with several unique features, highly reminiscent of Ammon's horn sclerosis as a final result, have rised the possibility that there is a link between trimethyltin neurotoxicity and other degenerative events for which an imbalance between neuronal inhibition/excitation has been proposed.However, there still exist a whole catalog of issues which await clarification.One of the greatest importance is how does trimethyltin reach the critical sites within the brain and what are they ? Available data concerning the long-term consequences related to trimethyltin neurotoxicity are also far from being completed.This review current data from in vitro and in vivo studies on neurotoxic effects of trimethyltin.Several hypotheses on mechanisms that may led to neuronal death induced by the toxin are presented.

5

Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: The role of NMDA and group I metabotropic glutamate receptors

71%

Zieminska E. , Lazarewicz J. W.

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nr 4

301-309

EN

Elevated homocysteine is a risk factor in cardiovascular diseases and neurodegeneration. Among the putative mechanisms of homocysteine-evoked neurotoxicity, disturbances in methylation processes and NMDA receptor-mediated excitotoxicity have been suggested. Our previous studies demonstrated that group I metabotropic glutamate receptors along with NMDA receptors participate in acute homocysteine-induced neuronal damage. In this study, using propidium iodide staining, we tested whether the same mechanism may mediate chronic homocysteine neurotoxicity. Our results confirmed that the application of D,L-homocysteine in micromolar concentrations for 3 days induces neurodegeneration in primary cultures of cerebellar granule neurons. Uncompetitive NMDA receptor antagonist MK-801, and mGlu1 or mGlu5 receptor antagonists (LY367385 and MPEP, respectively), given alone provided very limited neuroprotection. However, simultaneous application of the NMDA receptor antagonists MK-801, memantine or amantadine and MPEP almost completely prevented chronic homocysteine neurotoxicity. These findings suggest a novel therapeutic strategy to combat neurodegeneration induced by hyperhomocysteinemia comprising a combination of antagonists of group I metabotropic glutamate receptors and NMDA receptors.

6

Nicotinamide and 1-methylnicotinamide reduce homocysteine neurotoxicity in primary cultures of rat cerebellar granule cells

61%

Slomka M. , Zieminska E. , Lazarewicz J. W.

Acta Neurobiologiae Experimentalis

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2008

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tom 68

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nr 1

1-9

EN

Nicotinamide is an important cofactor in many metabolic pathways and a known neuroprotective substance, while its methylated product, 1-methylnicotinamide, is a suspected neurotoxin. Homocysteine is a risk factor in Alzheimer's disease and neurodegeneration, causing inhibition of methylation processes and inducing excitotoxicity. In this study, using primary cultures of rat cerebellar granule cells and propidium iodide staining, we investigated the neurotoxicity of nicotinamide and 1-methylnicotinamide, and their neuroprotective potential in acute and sub-acute homocysteine neurotoxicity. Our results demonstrated that nicotinamide and 1-methylnicotinamide applied for 24 h to cultures at concentrations of up to 25 mM had no effect on neuronal viability. Moreover, nicotinamide at concentrations of 5?20 mM and 1-methylnicotinamide at 1?10 mM applied to cells 24 h before, and for 24 h after an acute 30 min application of 25 mM D,L homocysteine, reduced neuronal damage. 1-Methylnicotinamide at concentrations of 250 and 500 ?M showed neuroprotective activity during a sub-acute 24-h exposure to 2.5 mM D,L-homocysteine, while 5 and 25 mM nicotinamide also evoked neuroprotection. These findings do not support suggestions that 1-methylnicotinamide may act as an endogenous neurotoxic agent; rather, they indicate the neuroprotective ability of nicotinamide and 1-methylnicotinamide in homocysteine neurotoxicity. The exact mechanisms of this neuroprotection are unclear and require further investigation.