Antagonistic interactions between dexamethasone and fluoxetine modulate morphodynamics and expression of cytokines in astrocytes
| Autor: | A. Devassy, M.M. Alawadi, Andreas Wolfram Henkel, Zoran B. Redzic, H. Alali |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Cell Survival medicine.medical_treatment Apoptosis Hippocampus Dexamethasone Rats Sprague-Dawley Cell Movement Fluoxetine Internal medicine medicine Extracellular Glial cell line-derived neurotrophic factor Animals Glial Cell Line-Derived Neurotrophic Factor Viability assay Glucocorticoids Cells Cultured Neurons biology Chemistry General Neuroscience Growth factor Coculture Techniques Endocrinology Astrocytes biology.protein Cytokines Interleukin-2 Female Selective Serotonin Reuptake Inhibitors Intracellular medicine.drug |
| Zdroj: | Neuroscience. 280:318-327 |
| ISSN: | 0306-4522 |
| Popis: | The "plasticity hypothesis" proposes that major depression is caused by morphological and biochemical modifications in neurons and astrocytes and those beneficial pharmacological effects of selective-serotonin-reuptake-inhibitors (SSRI) are at least partially associated with modifications of cellular communications between these cells. In this study we examined effects of the antidepressant fluoxetine on cultured astrocytes that were, in some cases, pretreated with dexamethasone, a cortisol analog known to trigger depressive disorder. Primary rat astrocytes were purified and treated with dexamethasone and the SSRI fluoxetine in physiological concentrations so that both drugs did not affect cell viability. Expression of interleukin-2 (IL-2) and glia-derived-neurotrophic-factor (GDNF) were analyzed and monitored and cell viability, apoptosis, cluster formation, particle-removing capacity and cell mobility were also monitored. Pre-studies without any drugs on mixed neuron-astrocyte co-cultures suggested that astrocytes interacted with neurons and other brain cells in vitro by actively assembling them into clusters. Treatment of purified astrocytes with dexamethasone significantly decreased their mobility compared to controls but had no effect on cluster formation. Dexamethasone-treated cells removed fewer extracellular particles derived from dead cells and cell debris. Both effects were abolished by simultaneous application of fluoxetine. Intracellular IL-2 increased, while GDNF amount expression was diminished following dexamethasone treatment. Simultaneous administration of fluoxetine reversed dexamethasone-triggered IL-2 elevation but had no effect on decreased GDNF concentration. These results suggest that mobility and growth factor equilibrium of astrocytes are affected by dexamethasone and by fluoxetine and that fluoxetine could reverse some changes induced by dexamethasone. |
| Databáze: | OpenAIRE |
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