Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1783605040400826368 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7609479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT lesiakatomj sequencingtheserotonergicneurontranslatomerevealsanewroleforfkbp5instress AT coffeykevin sequencingtheserotonergicneurontranslatomerevealsanewroleforfkbp5instress AT cohenjoshuah sequencingtheserotonergicneurontranslatomerevealsanewroleforfkbp5instress AT liangkatharinej sequencingtheserotonergicneurontranslatomerevealsanewroleforfkbp5instress AT chavkincharles sequencingtheserotonergicneurontranslatomerevealsanewroleforfkbp5instress AT neumaierjohnf sequencingtheserotonergicneurontranslatomerevealsanewroleforfkbp5instress |