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Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress

Serotonin is a key mediator of stress, anxiety, and depression, and novel therapeutic targets within serotonin neurons are needed to combat these disorders. To determine how stress alters the translational profile of serotonin neurons, we sequenced ribosome associated RNA from these neurons after re...

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Detalles Bibliográficos
Autores principales: Lesiak, Atom J., Coffey, Kevin, Cohen, Joshua H., Liang, Katharine J., Chavkin, Charles, Neumaier, John F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609479/
https://www.ncbi.nlm.nih.gov/pubmed/32366949
http://dx.doi.org/10.1038/s41380-020-0750-4
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author Lesiak, Atom J.
Coffey, Kevin
Cohen, Joshua H.
Liang, Katharine J.
Chavkin, Charles
Neumaier, John F.
author_facet Lesiak, Atom J.
Coffey, Kevin
Cohen, Joshua H.
Liang, Katharine J.
Chavkin, Charles
Neumaier, John F.
author_sort Lesiak, Atom J.
collection PubMed
description Serotonin is a key mediator of stress, anxiety, and depression, and novel therapeutic targets within serotonin neurons are needed to combat these disorders. To determine how stress alters the translational profile of serotonin neurons, we sequenced ribosome associated RNA from these neurons after repeated stress in male and female mice. We identified numerous sex- and stress-regulated genes. In particular, Fkbp5 mRNA, which codes for the glucocorticoid receptor co-chaperone protein FKBP51, was consistently upregulated in male and female mice following stress. Pretreatment with a selective FKBP51 inhibitor into the dorsal raphe prior to repeated forced swim stress decreased resulting stress-induced anhedonia. Our results support previous findings linking FKBP51 to stress-related disorders and provide the first evidence suggesting that FKBP51 function may be an important regulatory node integrating circulating stress hormones and serotonergic regulation of stress responses.
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spelling pubmed-76094792021-11-04 Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress Lesiak, Atom J. Coffey, Kevin Cohen, Joshua H. Liang, Katharine J. Chavkin, Charles Neumaier, John F. Mol Psychiatry Article Serotonin is a key mediator of stress, anxiety, and depression, and novel therapeutic targets within serotonin neurons are needed to combat these disorders. To determine how stress alters the translational profile of serotonin neurons, we sequenced ribosome associated RNA from these neurons after repeated stress in male and female mice. We identified numerous sex- and stress-regulated genes. In particular, Fkbp5 mRNA, which codes for the glucocorticoid receptor co-chaperone protein FKBP51, was consistently upregulated in male and female mice following stress. Pretreatment with a selective FKBP51 inhibitor into the dorsal raphe prior to repeated forced swim stress decreased resulting stress-induced anhedonia. Our results support previous findings linking FKBP51 to stress-related disorders and provide the first evidence suggesting that FKBP51 function may be an important regulatory node integrating circulating stress hormones and serotonergic regulation of stress responses. 2020-05-04 2021-09 /pmc/articles/PMC7609479/ /pubmed/32366949 http://dx.doi.org/10.1038/s41380-020-0750-4 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
Lesiak, Atom J.
Coffey, Kevin
Cohen, Joshua H.
Liang, Katharine J.
Chavkin, Charles
Neumaier, John F.
Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress
title Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress
title_full Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress
title_fullStr Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress
title_full_unstemmed Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress
title_short Sequencing the Serotonergic Neuron Translatome Reveals a New Role for Fkbp5 in Stress
title_sort sequencing the serotonergic neuron translatome reveals a new role for fkbp5 in stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609479/
https://www.ncbi.nlm.nih.gov/pubmed/32366949
http://dx.doi.org/10.1038/s41380-020-0750-4
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