@article{ff8a3dc79080404082c8bb9f4ef91670,
title = "Orphan receptor GPR158 controls stress-induced depression",
abstract = "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.",
author = "Sutton, {Laurie P.} and Cesare Orlandi and Chenghui Song and Oh, {Won Chan} and Muntean, {Brian S.} and Keqiang Xie and Alice Filippini and Xiangyang Xie and Rachel Satterfield and Yaeger, {Jazmine D.W.} and Renner, {Kenneth J.} and Young, {Samuel M.} and Baoji Xu and Hyungbae Kwon and Martemyanov, {Kirill A.}",
note = "Funding Information: We wish to thank Ms. Natalia Martemyanova for producing and maintaining mice examined in this study, Dr. Pablo Martinez for the help with the mass-spectrometry experiments and Dr. Massimiliano Aceti for his help with the analysis of spine density. This work was supported by NIH grants, MH105482 (KAM), HL105550 (KAM), DA019921 (KJR), MH107460 (H-BK), DC014093 (SMY), the University of Iowa and the Max Planck Society (SMY) and by the Canadian Institutes of Health Research Fellowship (LPS). National Institute of Mental Health MH105482 Kirill A Martemyanov National Heart, Lung, and Blood Institute HL105550 Kirill A Martemyanov National Institute of Mental Health MH107460 Hyungbae Kwon National Institute on Drug Abuse DA019921 Kenneth J Renner National Institute on Deafness and Other Communication Disorders DC014093 Samuel M Young Jr University of Iowa Samuel M Young Jr Max-Planck-Gesellschaft Samuel M Young Jr Canadian Institutes of Health Research Laurie P Sutton The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: We wish to thank Ms. Natalia Martemyanova for producing and maintaining mice examined in this study, Dr. Pablo Martinez for the help with the mass-spectrometry experiments and Dr. Massimiliano Aceti for his help with the analysis of spine density. This work was supported by NIH grants, MH105482 (KAM), HL105550 (KAM), DA019921 (KJR), MH107460 (H-BK), DC014093 (SMY), the University of Iowa and the Max Planck Society (SMY) and by the Canadian Institutes of Health Research Fellowship (LPS). Publisher Copyright: {\textcopyright} Sutton et al.",
year = "2018",
month = feb,
day = "8",
doi = "10.7554/eLife.33273",
language = "English (US)",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}