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Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress

Stress profoundly impacts the brain and increases the risk of developing a psychiatric disorder. The brain’s response to stress is mediated by a number of pathways that affect gene expression and protein function throughout the cell. Understanding how stress achieves such dramatic effects on the bra...

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Autores principales: Sillivan, Stephanie E., Jones, Meghan E., Jamieson, Sarah, Rumbaugh, Gavin, Miller, Courtney A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328204/
https://www.ncbi.nlm.nih.gov/pubmed/30629705
http://dx.doi.org/10.1371/journal.pone.0209846
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author Sillivan, Stephanie E.
Jones, Meghan E.
Jamieson, Sarah
Rumbaugh, Gavin
Miller, Courtney A.
author_facet Sillivan, Stephanie E.
Jones, Meghan E.
Jamieson, Sarah
Rumbaugh, Gavin
Miller, Courtney A.
author_sort Sillivan, Stephanie E.
collection PubMed
description Stress profoundly impacts the brain and increases the risk of developing a psychiatric disorder. The brain’s response to stress is mediated by a number of pathways that affect gene expression and protein function throughout the cell. Understanding how stress achieves such dramatic effects on the brain requires an understanding of the brain’s stress response pathways. The majority of studies focused on molecular changes have employed repeated or chronic stress paradigms to assess the long-term consequences of stress and have not taken an integrative genomic and/or proteomic approach. Here, we determined the lasting impact of a single stressful event (restraint) on the broad molecular profile of the basolateral amygdala complex (BLC), a key brain region mediating emotion, memory and stress. Molecular profiling performed thirty days post-restraint consisted of small RNA sequencing, RNA sequencing and quantitative mass spectrometry and identified long-lasting changes in microRNA (miRNA), messenger RNA (mRNA) and proteins. Alignment of the three datasets further delineated the regulation of stress-specific pathways which were validated by qPCR and Western Blot analysis. From this analysis, mir-29a-5p was identified as a putative regulator of stress-induced adaptations in the BLC. Further, a number of predicted mir-29a-5p targets are regulated at the mRNA and protein level. The concerted and long-lasting disruption of multiple molecular pathways in the amygdala by a single stress event is expected to be sufficient to alter behavioral responses to a wide array of future experiences, including exposure to additional stressors.
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spelling pubmed-63282042019-02-01 Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress Sillivan, Stephanie E. Jones, Meghan E. Jamieson, Sarah Rumbaugh, Gavin Miller, Courtney A. PLoS One Research Article Stress profoundly impacts the brain and increases the risk of developing a psychiatric disorder. The brain’s response to stress is mediated by a number of pathways that affect gene expression and protein function throughout the cell. Understanding how stress achieves such dramatic effects on the brain requires an understanding of the brain’s stress response pathways. The majority of studies focused on molecular changes have employed repeated or chronic stress paradigms to assess the long-term consequences of stress and have not taken an integrative genomic and/or proteomic approach. Here, we determined the lasting impact of a single stressful event (restraint) on the broad molecular profile of the basolateral amygdala complex (BLC), a key brain region mediating emotion, memory and stress. Molecular profiling performed thirty days post-restraint consisted of small RNA sequencing, RNA sequencing and quantitative mass spectrometry and identified long-lasting changes in microRNA (miRNA), messenger RNA (mRNA) and proteins. Alignment of the three datasets further delineated the regulation of stress-specific pathways which were validated by qPCR and Western Blot analysis. From this analysis, mir-29a-5p was identified as a putative regulator of stress-induced adaptations in the BLC. Further, a number of predicted mir-29a-5p targets are regulated at the mRNA and protein level. The concerted and long-lasting disruption of multiple molecular pathways in the amygdala by a single stress event is expected to be sufficient to alter behavioral responses to a wide array of future experiences, including exposure to additional stressors. Public Library of Science 2019-01-10 /pmc/articles/PMC6328204/ /pubmed/30629705 http://dx.doi.org/10.1371/journal.pone.0209846 Text en © 2019 Sillivan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sillivan, Stephanie E.
Jones, Meghan E.
Jamieson, Sarah
Rumbaugh, Gavin
Miller, Courtney A.
Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress
title Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress
title_full Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress
title_fullStr Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress
title_full_unstemmed Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress
title_short Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress
title_sort bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328204/
https://www.ncbi.nlm.nih.gov/pubmed/30629705
http://dx.doi.org/10.1371/journal.pone.0209846
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