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The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors
Alterations in serotonergic transmission have been related to a major predisposition to develop psychiatric pathologies, such as depression. We took advantage of tryptophan hydroxylase (TPH) 2 deficient rats, characterized by a complete absence of serotonin in the brain, to evaluate whether a vulner...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278285/ https://www.ncbi.nlm.nih.gov/pubmed/32547368 http://dx.doi.org/10.3389/fncel.2020.00128 |
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author | Sbrini, Giulia Brivio, Paola Peeva, Polina Mineva Todiras, Mihail Bader, Michael Alenina, Natalia Calabrese, Francesca |
author_facet | Sbrini, Giulia Brivio, Paola Peeva, Polina Mineva Todiras, Mihail Bader, Michael Alenina, Natalia Calabrese, Francesca |
author_sort | Sbrini, Giulia |
collection | PubMed |
description | Alterations in serotonergic transmission have been related to a major predisposition to develop psychiatric pathologies, such as depression. We took advantage of tryptophan hydroxylase (TPH) 2 deficient rats, characterized by a complete absence of serotonin in the brain, to evaluate whether a vulnerable genotype may influence the reaction to an acute stressor. In this context, we investigated if the glucocorticoid receptor (GR) genomic pathway activation was altered by the lack of serotonin in the central nervous system. Moreover, we analyzed the transcription pattern of the clock genes that can be affected by acute stressors. Adult wild type (TPH2(+/+)) and TPH2-deficient (TPH2(−/−)) male rats were sacrificed after exposure to one single session of acute restraint stress. Protein and gene expression analyses were conducted in the prefrontal cortex (PFC). The acute stress enhanced the translocation of GRs in the nucleus of TPH2(+/+) animals. This effect was blunted in TPH2(−/−) rats, suggesting an impairment of the GR genomic mechanism. This alteration was mirrored in the expression of GR-responsive genes: acute stress led to the up-regulation of GR-target gene expression in TPH2(+/+), but not in TPH2(−/−) animals. Finally, clock genes were differently modulated in the two genotypes after the acute restraint stress. Overall our findings suggest that the absence of serotonin within the brain interferes with the ability of the HPA axis to correctly modulate the response to acute stress, by altering the nuclear mechanisms of the GR and modulation of clock genes expression. |
format | Online Article Text |
id | pubmed-7278285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72782852020-06-15 The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors Sbrini, Giulia Brivio, Paola Peeva, Polina Mineva Todiras, Mihail Bader, Michael Alenina, Natalia Calabrese, Francesca Front Cell Neurosci Cellular Neuroscience Alterations in serotonergic transmission have been related to a major predisposition to develop psychiatric pathologies, such as depression. We took advantage of tryptophan hydroxylase (TPH) 2 deficient rats, characterized by a complete absence of serotonin in the brain, to evaluate whether a vulnerable genotype may influence the reaction to an acute stressor. In this context, we investigated if the glucocorticoid receptor (GR) genomic pathway activation was altered by the lack of serotonin in the central nervous system. Moreover, we analyzed the transcription pattern of the clock genes that can be affected by acute stressors. Adult wild type (TPH2(+/+)) and TPH2-deficient (TPH2(−/−)) male rats were sacrificed after exposure to one single session of acute restraint stress. Protein and gene expression analyses were conducted in the prefrontal cortex (PFC). The acute stress enhanced the translocation of GRs in the nucleus of TPH2(+/+) animals. This effect was blunted in TPH2(−/−) rats, suggesting an impairment of the GR genomic mechanism. This alteration was mirrored in the expression of GR-responsive genes: acute stress led to the up-regulation of GR-target gene expression in TPH2(+/+), but not in TPH2(−/−) animals. Finally, clock genes were differently modulated in the two genotypes after the acute restraint stress. Overall our findings suggest that the absence of serotonin within the brain interferes with the ability of the HPA axis to correctly modulate the response to acute stress, by altering the nuclear mechanisms of the GR and modulation of clock genes expression. Frontiers Media S.A. 2020-06-01 /pmc/articles/PMC7278285/ /pubmed/32547368 http://dx.doi.org/10.3389/fncel.2020.00128 Text en Copyright © 2020 Sbrini, Brivio, Peeva, Todiras, Bader, Alenina and Calabrese. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular Neuroscience Sbrini, Giulia Brivio, Paola Peeva, Polina Mineva Todiras, Mihail Bader, Michael Alenina, Natalia Calabrese, Francesca The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors |
title | The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors |
title_full | The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors |
title_fullStr | The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors |
title_full_unstemmed | The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors |
title_short | The Absence of Serotonin in the Brain Alters Acute Stress Responsiveness by Interfering With the Genomic Function of the Glucocorticoid Receptors |
title_sort | absence of serotonin in the brain alters acute stress responsiveness by interfering with the genomic function of the glucocorticoid receptors |
topic | Cellular Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278285/ https://www.ncbi.nlm.nih.gov/pubmed/32547368 http://dx.doi.org/10.3389/fncel.2020.00128 |
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