Dexamethasone attenuates kainate-induced AP-1 activation in rat brain

Unlap, Tino; Jope, Richard S.

doi:10.1016/0169-328x(94)90140-6

Cited by 40 publications

(13 citation statements)

References 27 publications

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“…The inhibition on c-Fos expression caused by glucocorticoids has been related to an interaction between proteins of the AP-1 complex and the glucocorticoid-receptor complex. Binding of activated glucocorticoid receptor to proteins of AP-1 complex (Fos or c-Jun) can decrease the AP-1 activity and thus consequently c-Fos expression (Unlap and Jope, 1994). However, the areas in which we detected an effect of dexamethasone could not be directly related to the areas with a high density of glucocorticoid receptors (mainly type II that are more sensitive to dexamethasone).…”

Section: Dexamethasonementioning

confidence: 61%

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Medeiros

Reis

Mello

2005

Neuropsychopharmacol

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Immobilization stress upregulates c-Fos expression in several CNS areas. Repeated stress or the use of drugs can modulate stressinduced c-Fos expression. Here, we investigated in 40 different areas of the rat brain the effects of dexamethasone (SDX, a synthetic glucocorticoid), diazepam (SBDZ, a benzodiazepine), and imipramine (IMI, an antidepressant) on the c-Fos expression induced by restraint stress. Wistar rats were divided into four groups and submitted to 20 days of daily injection of saline (three first groups) or imipramine, 15 mg/kg, i.p. On day 21, animals were submitted to injections of saline (somatosensory, SS), SDX (1 mg/kg, i.p.), SBDZ (5 mg/kg, i.p.), or IMI (15 mg/kg, i.p.) before being submitted to restraint. Immediately after stress, the animals were perfused and their brains processed with immunohistochemistry for c-Fos (Ab-5 Oncogene Science). Dexamethasone reduced stress-induced c-Fos expression in SS cortex, hippocampus, paraventricular nucleus of the hypothalamus (PVH), and locus coeruleus (LC), whereas diazepam reduced c-Fos staining in the SS cortex, hippocampus, bed nucleus of stria terminalis, septal area, and hypothalamus (preoptic area and supramammillary nucleus). Chronic administration of imipramine decreased staining in the hippocampus, PVH, and LC, while increasing it in the nucleus raphe pallidus. We conclude that dexamethasone, diazepam and imipramine differentially modulate stress-induced Fos expression. The present study provides an important comparative background that may help in the further understanding of the effects of these compounds and on the brain activation as well as on the behavioral, neuroendocrine, and autonomic responses to stress.

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Section: Dexamethasonementioning

confidence: 61%

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Medeiros

Reis

Mello

2005

Neuropsychopharmacol

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“…Other factors may also contribute to the decrease in expression of BDNF by corticosterone, such as that GR may downregulate BDNF expression by interacting with other transcription factors. Several AP-1 binding sites have been reported on the BDNF promoter (Hayes et al, 1997), and GR suppresses the activity of AP-1 (Unlap and Jope, 1994). In addition, all BDNF exons are regulated in an activity-dependent manner (Falkenberg et al, 1992;Timmusk and Metsis et al, 1994).…”

Section: Corticosterone Antidepressants and Bdnfmentioning

confidence: 99%

Antidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: Differential regulation of specific exons by antidepressants and corticosterone

2006

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Earlier studies have implicated BDNF in stress and in the mechanism of action of antidepressants. It has been shown that antidepressants upregulate, whereas corticosterone downregulates, BDNF expression in rat brain. Whether various classes of antidepressants reverse corticosterone-mediated downregulation of BDNF is unclear. Also not known is how antidepressants or corticosterone regulate BDNF expression. To clarify this, we examined the effects of various classes of antidepressants and corticosterone, alone and in combination, on the mRNA expression of total BDNF and of individual BDNF exons, in rat brain. Normal or corticosterone pellet-implanted (100 mg, 21 days) rats were injected with different classes of antidepressants, fluoxetine, desipramine, or phenelzine, intraperitoneally for 21 days and sacrificed 2 h after the last injection. mRNA expression of total BDNF and of exons I-IV was measured in frontal cortex and hippocampus. Given to normal rats, fluoxetine increased total BDNF mRNA only in hippocampus, whereas desipramine or phenelzine increased BDNF mRNA in both frontal cortex and hippocampus. When specifc exons were examined, desipramine increased expression of exons I and III in both brain areas, whereas phenelzine increased exon I in both frontal cortex and hippocampus but exon IV only in hippocampus. On the other hand, fluoxetine increased only exon II in hippocampus. Corticosterone treatment of normal rats decreased expression of total BDNF mRNA in both brain areas, specifically decreasing exons II and IV. Treatment with desipramine or phenelzine of corticosterone pellet-implanted rats reversed the corticosterone-induced decrease in total BDNF expression in both brain areas; however, fluoxetine reversed the decrease only partially in hippocampus. Interestingly, antidepressant treatment of corticosterone pellet-implanted rats increased only those specific exons that are increased during treatment of normal rats with each particular antidepressant. We found that although corticosterone and antidepressants both modulate BDNF expression, and antidepressants reverse the corticosterone-induced BDNF decrease, antidepressants and corticosterone differ in how they regulate the expression of BDNF exon(s).

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“…Ninety minutes after the LPS administration, the intact brain was removed, frozen in liquid nitrogen, and the brain cells prepared and isolated, and nuclear extracts were analyzed for NF-B activation as previously described. [15][16][17] Electrophoretic Mobility Shift Assay (EMSA) Nuclear extracts from the A-172 glioma cells and mouse brain cerebral cortical cells were harvested using standard procedures. 13,16,17 In brief, the cells from both sources were washed with 1 ml phosphate buffered saline (PBS) and incubated in PBS with EDTA 1% for 15 min at 4°C.…”

Section: Animals and Treatment (In Vivo Experiments)mentioning

confidence: 99%

“…[15][16][17] Electrophoretic Mobility Shift Assay (EMSA) Nuclear extracts from the A-172 glioma cells and mouse brain cerebral cortical cells were harvested using standard procedures. 13,16,17 In brief, the cells from both sources were washed with 1 ml phosphate buffered saline (PBS) and incubated in PBS with EDTA 1% for 15 min at 4°C. Cells were harvested with a cell scraper, transferred to 1.5 ml tubes, and centrifuged at 5,400 g for 10 sec.…”

Section: Animals and Treatment (In Vivo Experiments)mentioning

confidence: 99%

Ketamine suppresses endotoxin-induced NF-κB expression

Sakai

Ichiyama

Whitten

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: Ketamine reduces endotoxin-induced production of proinflammatory cytokines, including tumour necrosis factor-α (TNF), in several types of inflammatory cells, including monocytes and macrophages. Transcription of the genes that encode production of these proinflammatory cytokines is regulated by nuclear factor-kappa B (NF-6B). Cytoplasmic B protein is activated by endotoxin (LPS) as well as by TNF, allowing B protein to migrate into the cell nucleus to activate gene transcription for these inflammatory mediators. Because NF-6B is likely involved in brain injury and inflammatory neurodegenerative disease, such as multiple sclerosis, we examined whether ketamine inhibits LPS-induced activation of NF-6B in human glioma cells in vitro and intact mouse brain cells in vivo. Methods: Endotoxin-induced NF-6B expression in both the human glioma cells in vitro and the intact mouse brain cells in vivo was determined by electrophoretic mobility shift assays (EMSA) of nuclear extracts and measurement of NF-6B expression by densitometry. Endotoxin was injected intracerebroventricularly in vivo and intact brain was harvested. Klenow fragment labeling was used to identify NF-6B protein for both the in vivo and vitro experiments.Results: Endotoxin treatment increased NF-6B expression (P < 0.05) both in vivo and vitro compared with control (untreated) cells. Ketamine suppressed endotoxin-induced neuronal NF-6B activation in a dose-dependent manner (P < 0.05, except for the 10 -5 M concentration in vitro) both in vivo and vitro.Conclusion: Ketamine inhibits endotoxin-induced NF-6B expression in brain cells in vivo and vitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators.Objectif : La kétamine réduit la production de cytokines pro-inflammatoires induite par endotoxine, y compris le facteur nécrosant des tumeurs (TNF), dans certains types de cellules inflammatoires comprenant les monocytes et les macrophages. La transcription des gènes qui encodent la production de ces cytokines pro-inflammatoires est réglée par le facteur-kappa B nucléaire (NF-6B).La protéine cytoplasmique 6B est activée par l'endotoxine (LPS) et par le TNF et peut ainsi migrer dans le noyau cellulaire et activer la transcription génique pour ces médi-ateurs de l'inflammation. Comme le NF-6B participe probablement aux lésions cérébrales et aux maladies inflammatoires neurodégénératives, dont la sclérose en plaques, notre but était de savoir si la kétamine inhibe l'activation de NF-6B induit par LPS dans des cellules de gliome humain in vitro et dans des cellules cérébrales intactes de souris in vivo. Méthode : L'expression du NF-6B induite par endotoxine dans les cellules humaines in vitro et dans les cellules de souris in vivo a été déterminée par une étude de retardement de la mobilité électrophorétique (ERME) d'extraits nucléaires et la mesure de l'expression du NF-6B a été faite par densitométrie. L'endotoxine a été injectée dans les ventricules cérébraux in vivo et du tissu...

show abstract

Dexamethasone attenuates kainate-induced AP-1 activation in rat brain

Cited by 40 publications

References 27 publications

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Antidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: Differential regulation of specific exons by antidepressants and corticosterone

Ketamine suppresses endotoxin-induced NF-κB expression

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