title: Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes.
abstract: BACKGROUND
  The pharmacological actions of most antidepressants are ascribed to the modulation of serotonergic and/or noradrenergic transmission in the brain. During therapeutic treatment for major depression, fluoxetine, one of the most commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, accumulates in the brain, suggesting that fluoxetine may interact with additional targets. In this context, there is increasing evidence that astrocytes are involved in the pathophysiology of major depression.
  
  
  OBJECTIVE
  The aim of this study was to examine the effects of fluoxetine on the expression of neurotrophic/growth factors that have antidepressant properties and on glucose metabolism in cultured cortical astrocytes.
  
  
  RESULTS
  Treatment of astrocytes with fluoxetine and paroxetine, another SSRI antidepressant, upregulated brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and VGF mRNA expression. In contrast, the tricyclic antidepressants desipramine and imipramine did not affect the expression of these neurotrophic/growth factors. Analysis of the effects of fluoxetine on glucose metabolism revealed that fluoxetine reduces glycogen levels and increases glucose utilization and lactate release by astrocytes. Similar data were obtained with paroxetine, whereas imipramine and desipramine did not regulate glucose metabolism in this glial cell population. Our results also indicate that the effects of fluoxetine and paroxetine on glucose utilization, lactate release, and expression of BDNF, VEGF, and VGF are not mediated by serotonin-dependent mechanisms.
  
  
  CONCLUSIONS
  These data suggest that, by increasing the expression of specific astrocyte-derived neurotrophic factors and lactate release from astrocytes, fluoxetine may contribute to normalize the trophic and metabolic support to neurons in major depression.
authors.affiliation: Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
authors.forename: Igor
authors.initials: I
authors.lastname: Allaman
authors.forename: Hubert
authors.initials: H
authors.lastname: Fiumelli
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002478:Cells, Cultured; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D005947:Glucose; D036341:Intercellular Signaling Peptides and Proteins; D017367:Selective Serotonin Reuptake Inhibitors