title: Acute antidepressant treatment differently modulates ERK/MAPK activation in neurons and astrocytes of the adult mouse prefrontal cortex.
abstract: The onset of action of antidepressants (ADs) usually takes several weeks, but first molecular responses to these drugs may appear already after acute administration. The Extracellular Signal-regulated Kinase/Mitogen-Activated Protein Kinase (ERK/MAPK) signaling pathway is a target of ADs and an important pathway involved in cellular plasticity. In major depressive disorder (MDD), especially the prefrontal cortex (PFC) and hippocampus (Hip) are most likely affected in depressive patients and recent work revealed a hyperactivated ERK signaling in the rat PFC after chronic stress, a precipitating factor for MDD. Strong evidences support that not only neurons but also astrocytes participate in neuronal activity and may therefore additionally be a substrate of AD action. In this study, we show by Western blot that neither fluoxetine (FLX) nor desipramine (DMI) preferentially affects the activation of one of the two ERK isoforms, ERK1 and ERK2, with respect to the other. Further immunohistochemical analysis in the PFC revealed that basal levels of phospho-activated ERK (pERK) are mostly found in neurons in contrast to very few astrocytes. Both ADs can inhibit neuronal pERK as early as 15 min after drug administration with peculiar regional and layer specificities. Contrarily, at this time point none of the two ADs shows a clear modulation of astrocytic pERK. We propose that this mechanism of action of ADs may be protective against an exacerbated cortical ERK activity that may exert detrimental effects on susceptible neuronal populations. Our findings on acute effects of AD treatment in the adult mouse PFC encourage to examine further how this treatment might influence pERK in animal models of depression to identify early targets of AD action.
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany; Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany. Electronic address: barbara@mpipsykl.mpg.de.
authors.forename: B
authors.initials: B
authors.lastname: Di Benedetto
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Radecke
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: M V
authors.initials: MV
authors.lastname: Schmidt
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany; Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Rupprecht
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D003891:Desipramine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D003891:Desipramine