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Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice

Major depression is a common mental disorder that has been established to be associated with a decrease in serotonin and/or serotonin transporters in the brain. Peroxisome proliferator-activated receptor δ (PPARδ) has been introduced as a potential target for depression treatment. Telmisartan was re...

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Autores principales: Li, Yingxiao, Cheng, Kai-Chun, Liu, Keng-Fan, Peng, Wen-Huang, Cheng, Juei-Tang, Niu, Ho-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656622/
https://www.ncbi.nlm.nih.gov/pubmed/29070884
http://dx.doi.org/10.1038/s41598-017-14265-4
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author Li, Yingxiao
Cheng, Kai-Chun
Liu, Keng-Fan
Peng, Wen-Huang
Cheng, Juei-Tang
Niu, Ho-Shan
author_facet Li, Yingxiao
Cheng, Kai-Chun
Liu, Keng-Fan
Peng, Wen-Huang
Cheng, Juei-Tang
Niu, Ho-Shan
author_sort Li, Yingxiao
collection PubMed
description Major depression is a common mental disorder that has been established to be associated with a decrease in serotonin and/or serotonin transporters in the brain. Peroxisome proliferator-activated receptor δ (PPARδ) has been introduced as a potential target for depression treatment. Telmisartan was recently shown to activate PPARδ expression; therefore, the effectiveness of telmisartan in treating depression was investigated. In unpredictable chronic mild stress (UCMS) model, treatment with telmisartan for five weeks notably decrease in the time spent in the central and the reduced frequency of grooming and rearing in open filed test (OFT) and the decreased sucrose consumption in sucrose preference test (SPT) compared with the paradigms. Telmisartan also reversed the decrease in PPARδ and 5-HTT levels in the hippocampus of depression-like mice. Administration of PPARδ antagonist GSK0660 and direct infusion of sh-PPARδ into the brain blocked the effects of telmisartan on the improvement of depression-like behavior in these mice. Moreover, telmisartan enhanced the expression of PPARδ and 5HTT in H19-7 cells. In conclusion, the obtained results suggest that telmisartan improves symptoms of stress-induced depression in animals under chronic stress through activation of PPARδ. Therefore, telmisartan may be developed as a potential anti-depressant in the future.
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spelling pubmed-56566222017-10-31 Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice Li, Yingxiao Cheng, Kai-Chun Liu, Keng-Fan Peng, Wen-Huang Cheng, Juei-Tang Niu, Ho-Shan Sci Rep Article Major depression is a common mental disorder that has been established to be associated with a decrease in serotonin and/or serotonin transporters in the brain. Peroxisome proliferator-activated receptor δ (PPARδ) has been introduced as a potential target for depression treatment. Telmisartan was recently shown to activate PPARδ expression; therefore, the effectiveness of telmisartan in treating depression was investigated. In unpredictable chronic mild stress (UCMS) model, treatment with telmisartan for five weeks notably decrease in the time spent in the central and the reduced frequency of grooming and rearing in open filed test (OFT) and the decreased sucrose consumption in sucrose preference test (SPT) compared with the paradigms. Telmisartan also reversed the decrease in PPARδ and 5-HTT levels in the hippocampus of depression-like mice. Administration of PPARδ antagonist GSK0660 and direct infusion of sh-PPARδ into the brain blocked the effects of telmisartan on the improvement of depression-like behavior in these mice. Moreover, telmisartan enhanced the expression of PPARδ and 5HTT in H19-7 cells. In conclusion, the obtained results suggest that telmisartan improves symptoms of stress-induced depression in animals under chronic stress through activation of PPARδ. Therefore, telmisartan may be developed as a potential anti-depressant in the future. Nature Publishing Group UK 2017-10-25 /pmc/articles/PMC5656622/ /pubmed/29070884 http://dx.doi.org/10.1038/s41598-017-14265-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Yingxiao
Cheng, Kai-Chun
Liu, Keng-Fan
Peng, Wen-Huang
Cheng, Juei-Tang
Niu, Ho-Shan
Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice
title Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice
title_full Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice
title_fullStr Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice
title_full_unstemmed Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice
title_short Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice
title_sort telmisartan activates pparδ to improve symptoms of unpredictable chronic mild stress-induced depression in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656622/
https://www.ncbi.nlm.nih.gov/pubmed/29070884
http://dx.doi.org/10.1038/s41598-017-14265-4
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