Di Benedetto, B. and Radecke, J. and Schmidt, M. V. and Rupprecht, R. (2013) ACUTE ANTIDEPRESSANT TREATMENT DIFFERENTLY MODULATES ERK/MAPK ACTIVATION IN NEURONS AND ASTROCYTES OF THE ADULT MOUSE PREFRONTAL CORTEX. NEUROSCIENCE, 232. pp. 161-168. ISSN 0306-4522, 1873-7544
Full text not available from this repository. (Request a copy)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. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SIGNAL-REGULATED KINASE; DEPRESSIVE-LIKE BEHAVIOR; MOOD DISORDERS; CHRONIC STRESS; MAP KINASE; IN-VITRO; PATHWAYS; ERK1/2; BRAIN; FLUOXETINE; antidepressants; neuron; astrocyte; mouse; prefrontal cortex; ERK |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Apr 2020 09:34 |
| Last Modified: | 23 Apr 2020 09:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17003 |
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