title: Antagonistic interactions between dexamethasone and fluoxetine modulate morphodynamics and expression of cytokines in astrocytes.
abstract: 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.
authors.affiliation: Department of Physiology, Faculty of Medicine, Jabriya, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Electronic address: andreas@hsc.edu.kw.
authors.forename: A W
authors.initials: AW
authors.lastname: Henkel
authors.affiliation: Department of Physiology, Faculty of Medicine, Jabriya, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
authors.forename: H
authors.initials: H
authors.lastname: Alali
authors.affiliation: Department of Physiology, Faculty of Medicine, Jabriya, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
authors.forename: A
authors.initials: A
authors.lastname: Devassy
authors.affiliation: Department of Physiology, Faculty of Medicine, Jabriya, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
authors.forename: M M
authors.initials: MM
authors.lastname: Alawadi
authors.affiliation: Department of Physiology, Faculty of Medicine, Jabriya, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
authors.forename: Z B
authors.initials: ZB
authors.lastname: Redzic
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D003907:Dexamethasone; D005473:Fluoxetine; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005938:Glucocorticoids; D007376:Interleukin-2; D017367:Selective Serotonin Reuptake Inhibitors
keywords: antidepressant; astrocytes; depression; dexamethasone; fluoxetine