Orphan receptor GPR158 controls stress-induced depression
Stress can be a motivational force for decisive action and adapting to novel environment; whereas, exposure to chronic stress contributes to the development of depression and anxiety. However, the molecular mechanisms underlying stress-responsive behaviors are not fully understood. Here, we identifi...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2018-02-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/33273 |
id |
doaj-bc515a3f3b5740a393f3425dd4ab9426 |
---|---|
record_format |
Article |
spelling |
doaj-bc515a3f3b5740a393f3425dd4ab94262021-05-05T15:35:35ZengeLife Sciences Publications LtdeLife2050-084X2018-02-01710.7554/eLife.33273Orphan receptor GPR158 controls stress-induced depressionLaurie P Sutton0https://orcid.org/0000-0002-8694-2060Cesare Orlandi1Chenghui Song2https://orcid.org/0000-0003-3289-809XWon Chan Oh3Brian S Muntean4Keqiang Xie5Alice Filippini6Xiangyang Xie7Rachel Satterfield8Jazmine D W Yaeger9Kenneth J Renner10Samuel M Young Jr11https://orcid.org/0000-0002-7589-7612Baoji Xu12Hyungbae Kwon13Kirill A Martemyanov14https://orcid.org/0000-0002-9925-7599Department of Neuroscience, The Scripps Research Institute, Jupiter, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesMax Planck Florida Institute for Neuroscience, Jupiter, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesMax Planck Florida Institute for Neuroscience, Jupiter, United StatesCenter for Brain and Behavior Research, University of South Dakota, Vermillion, United States; Department of Biology, University of South Dakota, Vermillion, United StatesCenter for Brain and Behavior Research, University of South Dakota, Vermillion, United States; Department of Biology, University of South Dakota, Vermillion, United StatesMax Planck Florida Institute for Neuroscience, Jupiter, United States; Department of Anatomy and Cell Biology, University of Iowa, Iowa, United States; Aging Mind and Brain Initiative, University of Iowa, Iowa, United States; Department of Otolaryngology, Carver College of Medicine, University of Iowa, Iowa, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesMax Planck Florida Institute for Neuroscience, Jupiter, United States; Max Planck Institute of Neurobiology, Martinsried, GermanyDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesStress can be a motivational force for decisive action and adapting to novel environment; whereas, exposure to chronic stress contributes to the development of depression and anxiety. However, the molecular mechanisms underlying stress-responsive behaviors are not fully understood. Here, we identified the orphan receptor GPR158 as a novel regulator operating in the prefrontal cortex (PFC) that links chronic stress to depression. GPR158 is highly upregulated in the PFC of human subjects with major depressive disorder. Exposure of mice to chronic stress also increased GPR158 protein levels in the PFC in a glucocorticoid-dependent manner. Viral overexpression of GPR158 in the PFC induced depressive-like behaviors. In contrast GPR158 ablation, led to a prominent antidepressant-like phenotype and stress resiliency. We found that GPR158 exerts its effects via modulating synaptic strength altering AMPA receptor activity. Taken together, our findings identify a new player in mood regulation and introduce a pharmacological target for managing depression.https://elifesciences.org/articles/33273orphan receptorsdepressionGPCR signalingstress |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laurie P Sutton Cesare Orlandi Chenghui Song Won Chan Oh Brian S Muntean Keqiang Xie Alice Filippini Xiangyang Xie Rachel Satterfield Jazmine D W Yaeger Kenneth J Renner Samuel M Young Jr Baoji Xu Hyungbae Kwon Kirill A Martemyanov |
spellingShingle |
Laurie P Sutton Cesare Orlandi Chenghui Song Won Chan Oh Brian S Muntean Keqiang Xie Alice Filippini Xiangyang Xie Rachel Satterfield Jazmine D W Yaeger Kenneth J Renner Samuel M Young Jr Baoji Xu Hyungbae Kwon Kirill A Martemyanov Orphan receptor GPR158 controls stress-induced depression eLife orphan receptors depression GPCR signaling stress |
author_facet |
Laurie P Sutton Cesare Orlandi Chenghui Song Won Chan Oh Brian S Muntean Keqiang Xie Alice Filippini Xiangyang Xie Rachel Satterfield Jazmine D W Yaeger Kenneth J Renner Samuel M Young Jr Baoji Xu Hyungbae Kwon Kirill A Martemyanov |
author_sort |
Laurie P Sutton |
title |
Orphan receptor GPR158 controls stress-induced depression |
title_short |
Orphan receptor GPR158 controls stress-induced depression |
title_full |
Orphan receptor GPR158 controls stress-induced depression |
title_fullStr |
Orphan receptor GPR158 controls stress-induced depression |
title_full_unstemmed |
Orphan receptor GPR158 controls stress-induced depression |
title_sort |
orphan receptor gpr158 controls stress-induced depression |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-02-01 |
description |
Stress can be a motivational force for decisive action and adapting to novel environment; whereas, exposure to chronic stress contributes to the development of depression and anxiety. However, the molecular mechanisms underlying stress-responsive behaviors are not fully understood. Here, we identified the orphan receptor GPR158 as a novel regulator operating in the prefrontal cortex (PFC) that links chronic stress to depression. GPR158 is highly upregulated in the PFC of human subjects with major depressive disorder. Exposure of mice to chronic stress also increased GPR158 protein levels in the PFC in a glucocorticoid-dependent manner. Viral overexpression of GPR158 in the PFC induced depressive-like behaviors. In contrast GPR158 ablation, led to a prominent antidepressant-like phenotype and stress resiliency. We found that GPR158 exerts its effects via modulating synaptic strength altering AMPA receptor activity. Taken together, our findings identify a new player in mood regulation and introduce a pharmacological target for managing depression. |
topic |
orphan receptors depression GPCR signaling stress |
url |
https://elifesciences.org/articles/33273 |
work_keys_str_mv |
AT lauriepsutton orphanreceptorgpr158controlsstressinduceddepression AT cesareorlandi orphanreceptorgpr158controlsstressinduceddepression AT chenghuisong orphanreceptorgpr158controlsstressinduceddepression AT wonchanoh orphanreceptorgpr158controlsstressinduceddepression AT briansmuntean orphanreceptorgpr158controlsstressinduceddepression AT keqiangxie orphanreceptorgpr158controlsstressinduceddepression AT alicefilippini orphanreceptorgpr158controlsstressinduceddepression AT xiangyangxie orphanreceptorgpr158controlsstressinduceddepression AT rachelsatterfield orphanreceptorgpr158controlsstressinduceddepression AT jazminedwyaeger orphanreceptorgpr158controlsstressinduceddepression AT kennethjrenner orphanreceptorgpr158controlsstressinduceddepression AT samuelmyoungjr orphanreceptorgpr158controlsstressinduceddepression AT baojixu orphanreceptorgpr158controlsstressinduceddepression AT hyungbaekwon orphanreceptorgpr158controlsstressinduceddepression AT kirillamartemyanov orphanreceptorgpr158controlsstressinduceddepression |
_version_ |
1721459945410396160 |