Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine
Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e., fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD...
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Frontiers Media S.A.
2022-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.993449/full |
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author | Rodolphe H. Lebeau Indira Mendez-David Laura Kucynski-Noyau Céline Henry David Attali Marion Plaze Romain Colle Romain Colle Emmanuelle Corruble Emmanuelle Corruble Alain M. Gardier Raphaël Gaillard Jean-Philippe Guilloux Denis J. David |
author_facet | Rodolphe H. Lebeau Indira Mendez-David Laura Kucynski-Noyau Céline Henry David Attali Marion Plaze Romain Colle Romain Colle Emmanuelle Corruble Emmanuelle Corruble Alain M. Gardier Raphaël Gaillard Jean-Philippe Guilloux Denis J. David |
author_sort | Rodolphe H. Lebeau |
collection | DOAJ |
description | Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e., fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ∼50–63% in patients with pharmaco-resistant depression. Nevertheless, the need to develop reliable treatment response predictors to guide personalized AD strategies and supplement clinical observation is becoming a pressing clinical objective. Here, we propose to establish a proteomic peripheral biomarkers signature of ECT response in an anxio/depressive animal model of non-response to AD. Using an emotionality score based on the analysis complementary behavioral tests of anxiety/depression (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35 μg/ml, Cort model) in C57BL/6JRj male mice induced an anxiety/depressive-like behavior. A 28-day chronic fluoxetine treatment (Flx, 18 mg/kg/day) reduced corticosterone-induced increase in emotional behavior. A 50% decrease in emotionality score threshold before and after Flx, was used to separate Flx-responding mice (Flx-R, n = 18), or Flx non-responder mice (Flx-NR, n = 7). Then, Flx-NR mice received seven sessions of electroconvulsive seizure (ECS, equivalent to ECT in humans) and blood was collected before and after ECS treatment. Chronic ECS normalized the elevated emotionality observed in Flx-NR mice. Then, proteins were extracted from peripheral blood mononuclear cells (PBMCs) and isolated for proteomic analysis using a high-resolution MS Orbitrap. Data are available via ProteomeXchange with identifier PXD037392. The proteomic analysis revealed a signature of 33 peripheral proteins associated with response to ECS (7 down and 26 upregulated). These proteins were previously associated with mental disorders and involved in regulating pathways which participate to the depressive disorder etiology. |
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spelling | doaj.art-c25236a1172841aaa8b0611b183552a72022-12-22T03:56:30ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.993449993449Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetineRodolphe H. Lebeau0Indira Mendez-David1Laura Kucynski-Noyau2Céline Henry3David Attali4Marion Plaze5Romain Colle6Romain Colle7Emmanuelle Corruble8Emmanuelle Corruble9Alain M. Gardier10Raphaël Gaillard11Jean-Philippe Guilloux12Denis J. David13Batiment Henri Moissan, CESP-Inserm, MOODS Team, Université Paris-Saclay, Orsay, FranceBatiment Henri Moissan, CESP-Inserm, MOODS Team, Université Paris-Saclay, Orsay, FranceBatiment Henri Moissan, CESP-Inserm, MOODS Team, Université Paris-Saclay, Orsay, FrancePAPPSO, Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceCentre Hospitalier Sainte Anne, Service Hospitalo-Universitaire, Paris, FranceCentre Hospitalier Sainte Anne, Service Hospitalo-Universitaire, Paris, FranceUniversité Paris-Saclay, Faculté de Médecine, CESP-Inserm, MOODS Team, Le Kremlin Bicêtre, FranceService Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, FranceUniversité Paris-Saclay, Faculté de Médecine, CESP-Inserm, MOODS Team, Le Kremlin Bicêtre, FranceService Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, FranceBatiment Henri Moissan, CESP-Inserm, MOODS Team, Université Paris-Saclay, Orsay, FranceCentre Hospitalier Sainte Anne, Service Hospitalo-Universitaire, Paris, FranceBatiment Henri Moissan, CESP-Inserm, MOODS Team, Université Paris-Saclay, Orsay, FranceBatiment Henri Moissan, CESP-Inserm, MOODS Team, Université Paris-Saclay, Orsay, FranceMajor depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e., fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ∼50–63% in patients with pharmaco-resistant depression. Nevertheless, the need to develop reliable treatment response predictors to guide personalized AD strategies and supplement clinical observation is becoming a pressing clinical objective. Here, we propose to establish a proteomic peripheral biomarkers signature of ECT response in an anxio/depressive animal model of non-response to AD. Using an emotionality score based on the analysis complementary behavioral tests of anxiety/depression (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35 μg/ml, Cort model) in C57BL/6JRj male mice induced an anxiety/depressive-like behavior. A 28-day chronic fluoxetine treatment (Flx, 18 mg/kg/day) reduced corticosterone-induced increase in emotional behavior. A 50% decrease in emotionality score threshold before and after Flx, was used to separate Flx-responding mice (Flx-R, n = 18), or Flx non-responder mice (Flx-NR, n = 7). Then, Flx-NR mice received seven sessions of electroconvulsive seizure (ECS, equivalent to ECT in humans) and blood was collected before and after ECS treatment. Chronic ECS normalized the elevated emotionality observed in Flx-NR mice. Then, proteins were extracted from peripheral blood mononuclear cells (PBMCs) and isolated for proteomic analysis using a high-resolution MS Orbitrap. Data are available via ProteomeXchange with identifier PXD037392. The proteomic analysis revealed a signature of 33 peripheral proteins associated with response to ECS (7 down and 26 upregulated). These proteins were previously associated with mental disorders and involved in regulating pathways which participate to the depressive disorder etiology.https://www.frontiersin.org/articles/10.3389/fphar.2022.993449/fullelectroconvulsive therapyfluoxetinenon-responseperipheral biomarkersmajor depressive disorderdifficult to treat depression |
spellingShingle | Rodolphe H. Lebeau Indira Mendez-David Laura Kucynski-Noyau Céline Henry David Attali Marion Plaze Romain Colle Romain Colle Emmanuelle Corruble Emmanuelle Corruble Alain M. Gardier Raphaël Gaillard Jean-Philippe Guilloux Denis J. David Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine Frontiers in Pharmacology electroconvulsive therapy fluoxetine non-response peripheral biomarkers major depressive disorder difficult to treat depression |
title | Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine |
title_full | Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine |
title_fullStr | Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine |
title_full_unstemmed | Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine |
title_short | Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine |
title_sort | peripheral proteomic changes after electroconvulsive seizures in a rodent model of non response to chronic fluoxetine |
topic | electroconvulsive therapy fluoxetine non-response peripheral biomarkers major depressive disorder difficult to treat depression |
url | https://www.frontiersin.org/articles/10.3389/fphar.2022.993449/full |
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