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Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling

Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize durin...

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Autores principales: Brivio, Paola, Sbrini, Giulia, Corsini, Giulia, Paladini, Maria Serena, Racagni, Giorgio, Molteni, Raffaella, Calabrese, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503736/
https://www.ncbi.nlm.nih.gov/pubmed/32872446
http://dx.doi.org/10.3390/ijms21176261
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author Brivio, Paola
Sbrini, Giulia
Corsini, Giulia
Paladini, Maria Serena
Racagni, Giorgio
Molteni, Raffaella
Calabrese, Francesca
author_facet Brivio, Paola
Sbrini, Giulia
Corsini, Giulia
Paladini, Maria Serena
Racagni, Giorgio
Molteni, Raffaella
Calabrese, Francesca
author_sort Brivio, Paola
collection PubMed
description Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize during symptoms remission, facilitating the relapse to the pathology. Hence, we investigated the long-lasting effects of chronic restraint stress (CRS) and its influence on the modifications induced by the exposure to a second hit on brain-derived neurotrophic factor (BDNF) signaling in the prefrontal cortex (PFC). We exposed adult male Sprague Dawley rats to 4 weeks of CRS, we left them undisturbed for the subsequent 3 weeks, and then we exposed animals to one hour of acute restraint stress (ARS). We found that CRS influenced the release of corticosterone induced by ARS and inhibited the ability of ARS to activate mature BDNF, its receptor Tropomyosin receptor kinase B (TRKB), and their associated intracellular cascades: the TRKB-PI3K-AKT), the MEK-MAPK/ERK, and the Phospholipase C γ (PLCγ) pathways, positively modulated by ARS in non-stressed animals. These results suggest that CRS induces protracted and detrimental consequences that interfere with the ability of PFC to cope with a challenging situation.
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spelling pubmed-75037362020-09-27 Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling Brivio, Paola Sbrini, Giulia Corsini, Giulia Paladini, Maria Serena Racagni, Giorgio Molteni, Raffaella Calabrese, Francesca Int J Mol Sci Article Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize during symptoms remission, facilitating the relapse to the pathology. Hence, we investigated the long-lasting effects of chronic restraint stress (CRS) and its influence on the modifications induced by the exposure to a second hit on brain-derived neurotrophic factor (BDNF) signaling in the prefrontal cortex (PFC). We exposed adult male Sprague Dawley rats to 4 weeks of CRS, we left them undisturbed for the subsequent 3 weeks, and then we exposed animals to one hour of acute restraint stress (ARS). We found that CRS influenced the release of corticosterone induced by ARS and inhibited the ability of ARS to activate mature BDNF, its receptor Tropomyosin receptor kinase B (TRKB), and their associated intracellular cascades: the TRKB-PI3K-AKT), the MEK-MAPK/ERK, and the Phospholipase C γ (PLCγ) pathways, positively modulated by ARS in non-stressed animals. These results suggest that CRS induces protracted and detrimental consequences that interfere with the ability of PFC to cope with a challenging situation. MDPI 2020-08-29 /pmc/articles/PMC7503736/ /pubmed/32872446 http://dx.doi.org/10.3390/ijms21176261 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brivio, Paola
Sbrini, Giulia
Corsini, Giulia
Paladini, Maria Serena
Racagni, Giorgio
Molteni, Raffaella
Calabrese, Francesca
Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling
title Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling
title_full Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling
title_fullStr Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling
title_full_unstemmed Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling
title_short Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling
title_sort chronic restraint stress inhibits the response to a second hit in adult male rats: a role for bdnf signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503736/
https://www.ncbi.nlm.nih.gov/pubmed/32872446
http://dx.doi.org/10.3390/ijms21176261
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