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microRNA regulation of persistent stress-enhanced memory
Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883139/ https://www.ncbi.nlm.nih.gov/pubmed/31142820 http://dx.doi.org/10.1038/s41380-019-0432-2 |
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author | Sillivan, Stephanie E. Jamieson, Sarah de Nijs, Laurence Jones, Meghan Snijders, Clara Klengel, Torsten Joseph, Nadine F. Krauskopf, Julian Kleinjans, Jos Vinkers, Christiaan H. Boks, Marco P.M. Geuze, Elbert Vermetten, Eric Berretta, Sabina Ressler, Kerry J. Rutten, Bart P.F. Rumbaugh, Gavin Miller, Courtney A. |
author_facet | Sillivan, Stephanie E. Jamieson, Sarah de Nijs, Laurence Jones, Meghan Snijders, Clara Klengel, Torsten Joseph, Nadine F. Krauskopf, Julian Kleinjans, Jos Vinkers, Christiaan H. Boks, Marco P.M. Geuze, Elbert Vermetten, Eric Berretta, Sabina Ressler, Kerry J. Rutten, Bart P.F. Rumbaugh, Gavin Miller, Courtney A. |
author_sort | Sillivan, Stephanie E. |
collection | PubMed |
description | Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like characteristics in a subset of mice, including persistently enhanced memory and heightened cFos in the basolateral amygdala complex (BLC) with retrieval of the remote (30 day old) stress memory. Here the contribution of BLC microRNAs (miRNAs) to stress-enhanced memory was investigated because of the molecular complexity they achieve through their ability to regulate multiple targets simultaneously. We performed small-RNA sequencing (smRNA-Seq) and quantitative proteomics on BLC tissue collected from mice one month after SEFL and identified persistently changed microRNAs, including mir-135b-5p, and proteins associated with PTSD-like heightened fear expression. Viral-mediated overexpression of mir-135b-5p in the BLC of stress-resilient animals enhanced remote fear memory expression and promoted spontaneous renewal 14 days after extinction. Conversely, inhibition of BLC mir-135b-5p in stress-susceptible animals had the opposite effect, promoting a resilient-like phenotype. mir-135b-5p is highly conserved across mammals and was detected in postmortem human amygdala, as well as human serum samples. The mir-135b passenger strand, mir-135b-3p, was significantly elevated in serum from PTSD military veterans, relative to combat-exposed control subjects. Thus, miR-135b-5p may be an important therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic. |
format | Online Article Text |
id | pubmed-6883139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68831392019-11-30 microRNA regulation of persistent stress-enhanced memory Sillivan, Stephanie E. Jamieson, Sarah de Nijs, Laurence Jones, Meghan Snijders, Clara Klengel, Torsten Joseph, Nadine F. Krauskopf, Julian Kleinjans, Jos Vinkers, Christiaan H. Boks, Marco P.M. Geuze, Elbert Vermetten, Eric Berretta, Sabina Ressler, Kerry J. Rutten, Bart P.F. Rumbaugh, Gavin Miller, Courtney A. Mol Psychiatry Article Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like characteristics in a subset of mice, including persistently enhanced memory and heightened cFos in the basolateral amygdala complex (BLC) with retrieval of the remote (30 day old) stress memory. Here the contribution of BLC microRNAs (miRNAs) to stress-enhanced memory was investigated because of the molecular complexity they achieve through their ability to regulate multiple targets simultaneously. We performed small-RNA sequencing (smRNA-Seq) and quantitative proteomics on BLC tissue collected from mice one month after SEFL and identified persistently changed microRNAs, including mir-135b-5p, and proteins associated with PTSD-like heightened fear expression. Viral-mediated overexpression of mir-135b-5p in the BLC of stress-resilient animals enhanced remote fear memory expression and promoted spontaneous renewal 14 days after extinction. Conversely, inhibition of BLC mir-135b-5p in stress-susceptible animals had the opposite effect, promoting a resilient-like phenotype. mir-135b-5p is highly conserved across mammals and was detected in postmortem human amygdala, as well as human serum samples. The mir-135b passenger strand, mir-135b-3p, was significantly elevated in serum from PTSD military veterans, relative to combat-exposed control subjects. Thus, miR-135b-5p may be an important therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic. 2019-05-29 2020-05 /pmc/articles/PMC6883139/ /pubmed/31142820 http://dx.doi.org/10.1038/s41380-019-0432-2 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Sillivan, Stephanie E. Jamieson, Sarah de Nijs, Laurence Jones, Meghan Snijders, Clara Klengel, Torsten Joseph, Nadine F. Krauskopf, Julian Kleinjans, Jos Vinkers, Christiaan H. Boks, Marco P.M. Geuze, Elbert Vermetten, Eric Berretta, Sabina Ressler, Kerry J. Rutten, Bart P.F. Rumbaugh, Gavin Miller, Courtney A. microRNA regulation of persistent stress-enhanced memory |
title | microRNA regulation of persistent stress-enhanced memory |
title_full | microRNA regulation of persistent stress-enhanced memory |
title_fullStr | microRNA regulation of persistent stress-enhanced memory |
title_full_unstemmed | microRNA regulation of persistent stress-enhanced memory |
title_short | microRNA regulation of persistent stress-enhanced memory |
title_sort | microrna regulation of persistent stress-enhanced memory |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883139/ https://www.ncbi.nlm.nih.gov/pubmed/31142820 http://dx.doi.org/10.1038/s41380-019-0432-2 |
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