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- Dahlqvist, Per, et al.
(författare)
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Effects of postischemic environment on transcription factor and serotonin receptor expression after permanent focal cortical ischemia in rats
- 2003
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Ingår i: Neuroscience. - 1873-7544 .- 0306-4522. ; 119:3, s. 643-652
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Tidskriftsartikel (refereegranskat)abstract
- Housing rats in an enriched environment improves functional outcome after ischemic stroke, this may reflect neuronal plasticity in brain regions outside the lesion. Which components of the enriched environment that are of greatest importance for recovery after brain ischemia is uncertain. We have previously found that enriched environment and social interaction alone both improve functional recovery after focal cerebral ischemia, compared with isolated housing with voluntary wheel-running. In this study, the aim was to separate components of the enriched environment and investigate the effects on some potential mediators of improved functional recovery; such as the inducible transcription factors nerve growth factor-induced gene A (NGFI-A) and NGFI-B, and the glucocorticoid and serotonin systems. After permanent middle cerebral artery occlusion, rats were divided into four groups: individually housed with no equipment (deprived group), individually housed with free access to a running wheel (running group), housed together in a large cage with no equipment (social group) or in a large cage furnished with exchangeable bars, chains and other objects (enriched group). mRNA expression of inducible transcription factors, serotonin and glucocorticoid receptors was determined with in situ hybridisation 1 month after cerebral ischemia. Rats housed in enriched or social environments showed significantly higher mRNA expression of NGFI-A and NGFI-B in cortical regions outside the lesion and in the CA1 (cornu ammonis region of the hippocampus), compared with isolated rats with or without a running wheel. NGFI-A and NGFI-B mRNA expression in cortex and in CA1 was significantly correlated to functional outcome. 5-Hydroxytryptamine receptor 1A (5-HT1A) mRNA expression and binding, as well as 5-HT2A receptor mRNA expression were decreased in the hippocampus (CA4 region) of the running wheel rats. Mineralocorticoid receptor gene expression was increased in the dentate gyrus amongst wheel-running rats. No group differences were found in plasma corticosterone levels or mRNA levels of glucocorticoid receptor, corticotropin-releasing hormone, 5-HT2C or c-fos. In conclusion, we have found that social interaction is a major component of the enriched environment regarding the effects on NGFI-A and NGFI-B expression. These transcription factors may be important mediators of improved functional recovery after brain infarctions, induced by environmental enrichment. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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| 2. |
- Shamloo, M., et al.
(författare)
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Subcellular distribution and autophosphorylation of calcium/calmodulin- dependent protein kinase II-α in rat hippocampus in a model of ischemic tolerance
- 2000
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Ingår i: Neuroscience. - 0306-4522. ; 96:4, s. 665-674
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Tidskriftsartikel (refereegranskat)abstract
- A brief period of sublethal ischemia induces resistance to a subsequent, otherwise lethal, ischemic insult, a process named ischemic tolerance or preconditioning. A persistently disturbed cell signaling during reperfusion after cerebral ischemia has been proposed to contribute to ischemic cell death. Here, we report on the effect of ischemic preconditioning on the levels of the regulatory α-subunit of calcium/calmodulin protein kinase II and its phosphorylation in the hippocampal CA1 region. We found that during and following lethal cerebral ischemia, calcium/calmodulin protein kinase II- α is persistently translocated to cell membranes, where it becomes phosphorylated at threonine 286. In contrast, in the preconditioned brains the translocation and phosphorylation are transient and return to preischemic values after one day of reperfusion. At this time of reperfusion, the total level of calcium/calmodulin protein kinase II-α is significantly lower in preconditioned animals compared to the sham and non-conditioned animals. After one day of reperfusion, the level of calcium/calmodulin protein kinase II-α messenger RNA decreases in the non-conditioned brains, whereas it is unchanged in preconditioned brains. We conclude that, during and after ischemia, calcium/calmodulin protein kinase II-α is translocated to cell membranes and becomes phosphorylated at threonine 286. This could detrimentally influence cell survival by changing receptor function and ion channel conductance. Ischemic preconditioning prevents the persistent presence of calcium/calmodulin protein kinase II-α at cell membranes, presumably by enhancing its degradation, which could be part of a neuroprotective mechanism of ischemic tolerance. (C) 2000 IBRO.
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| 3. |
- Sjögreen, B., et al.
(författare)
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Mitogen activated protein kinase inhibition by PD98059 blocks nerve growth factor stimulated axonal outgrowth from adult mouse dorsal root ganglia in vitro
- 2000
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Ingår i: Neuroscience. - 0306-4522. ; 100:2, s. 407-416
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Tidskriftsartikel (refereegranskat)abstract
- Nerve growth factor stimulated axonal outgrowth from explanted mouse dorsal root ganglia is dependent on mitogen activated protein kinase. PD98059 ([2-(2'amino-3'-methoxyphenyl)-oxanaphthalen-4-one]) blocks mitogen activated protein kinase by inhibiting its immediate upstream activator, mitogen activated protein kinase kinase (also known as MEK). Here we used PD98059 to study the role of mitogen activated protein kinase in the axonal outgrowth of adult dorsal root ganglia explants. Whereas PD98059 at 50μM left spontaneous axonal outgrowth unaffected, it markedly inhibited nerve growth factor stimulated axon growth when assessed after two days in culture. A mitogen activated protein kinase assay and immunoblotting using antibodies discriminating between activated and inactivated kinase, both confirmed that PD98059 reduced the amount of activated enzyme in nerve growth factor stimulated preparations, while the total amounts of the kinase remained unchanged. Immunohistochemistry revealed the presence of neuronal mitogen activated protein kinase kinase and mitogen activated protein kinase itself. The latter enzyme was found to be activated in the growing axons, as seen by whole-mount labelling. At the ganglionic level activated mitogen activated protein kinase was preferentially detected in satellite cells.The results show that nerve growth factor stimulated axonal outgrowth in vitro from adult mouse dorsal root ganglia utilizes the mitogen activated protein kinase pathway. Copyright (C) 2000 IBRO.
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