title: Paroxetine rapidly modulates the expression of brain-derived neurotrophic factor mRNA and protein in a human glioblastoma-astrocytoma cell line.
abstract: Neuronal upregulation of the brain-derived neurotrophic factor (BDNF) gene appears to be a crucial factor for the efficacy of antidepressants. However, besides neurons, little information is present on the modulation of BDNF by antidepressants at RNA and protein levels in other cell types of the central nervous system. Glial cells are able to store and release BDNF, and it has been hypothesized that glial dysfunction may contribute to the etiopathogenesis of depression. Thus, in this study we used the human glioblastoma-astrocytoma cell line U87 exposed to the antidepressant drug paroxetine, and evaluated BDNF mRNA and protein expression. In addition, since the BDNF gene can be posttranscriptionally modulated by a family of microRNA, we also evaluated the levels for one of these microRNA (miR-30a-5p) in the U87 cell line during paroxetine treatment. We found that paroxetine treatment rapidly increased BDNF in U87 cells, resulting from an induction of BDNF mRNA expression and de novo protein synthesis, and that these increases occurred in a time-dependent manner. Paroxetine effects were evident at 6 h of incubation for BDNF mRNA and at 12 h for BDNF protein. In addition, the transcriptional BDNF inhibitor miR-30a-5p was also overexpressed at 6 and 12 h of paroxetine incubation. These findings indicate that the U87 cell line, an in vitro model of glial cells, rapidly responds to paroxetine by increasing BDNF production, and that these effects are potentially limited by microRNA induction. These data may contribute to explain the action of paroxetine on cells of nonneuronal origin.
authors.affiliation: IRCCS Santa Lucia Foundation, Rome, Italy. f.angelucci@hsantalucia.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelucci
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Croce
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dinallo
authors.forename: Paolo
authors.initials: P
authors.lastname: Gravina
authors.forename: Paola
authors.initials: P
authors.lastname: Bossù
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D017374:Paroxetine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D035683:MicroRNAs; D017374:Paroxetine; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors; C546086:MIRN30b microRNA, human