Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1
Depression is a major cause of disease burden and severely impairs well-being of patients around the globe. Geniposide (GP) has been revealed to play a significant role in depression treatment. Of note, RNA sequencing of this study identified highly expressed long non-coding RNA Six3os1 in response...
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doaj-4cea5f4fb5d54557a69749765dec3a652020-11-25T03:06:09ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-10-01810.3389/fcell.2020.553728553728Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1Tianyu Zou0Kazuo Sugimoto1Jielin Zhang2Yongxiu Liu3Yiming Zhang4Hao Liang5Yinan Jiang6Jing Wang7Guoxiang Duan8Cheng Mei9Department of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Dermatology, Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology, Harbin, ChinaDepartment of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Encephalopathy, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepression is a major cause of disease burden and severely impairs well-being of patients around the globe. Geniposide (GP) has been revealed to play a significant role in depression treatment. Of note, RNA sequencing of this study identified highly expressed long non-coding RNA Six3os1 in response to GP treatment. Thus, we aim to explore how GP affected chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in mice in vivo and in vitro and the downstream molecular mechanism related to Six3os1. The relationship of Six3os1, miR-511-3p and Fezf1 was evaluated by dual-luciferase reporter gene assay, RIP assay, and RNA pulling down assay. Ectopic expression and knockdown experiments were developed in CUMS-induced mice and neurons with or without GP treatment. In vitro experiments and behavioral tests were conducted to examine alteration of CUMS-triggered oxidative stress following different interferences. The experimental data validated that GP treatment resulted in high expression of Six3os1 and Fezf1 and poor expression of miR-511-3p in CUMS-induced neurons. Six3os1 activated the AKT signaling pathway by upregulating miR-511-3p-targeted Fezf1. Either GP treatment or overexpression of Six3os1 or Fezf1 alleviated depression-like behaviors of CUMS-induced mice. GP treatment, miR-511-3p inhibition or overexpression of Six3os1 or Fezf1 not only reduced oxidative stress in CUMS-induced mice and neurons, but also reduced CUMS-induced neuronal apoptosis. Collectively, GP treatment-mediated Six3os1 upregulation ameliorated oxidative stress of mice with depression-like behaviors via the miR-511-3p/Fezf1/AKT axis.https://www.frontiersin.org/articles/10.3389/fcell.2020.553728/fulldepressiongeniposideSix3os1miR-511-3pFEZF1Akt signaling pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tianyu Zou Kazuo Sugimoto Jielin Zhang Yongxiu Liu Yiming Zhang Hao Liang Yinan Jiang Jing Wang Guoxiang Duan Cheng Mei |
spellingShingle |
Tianyu Zou Kazuo Sugimoto Jielin Zhang Yongxiu Liu Yiming Zhang Hao Liang Yinan Jiang Jing Wang Guoxiang Duan Cheng Mei Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1 Frontiers in Cell and Developmental Biology depression geniposide Six3os1 miR-511-3p FEZF1 Akt signaling pathway |
author_facet |
Tianyu Zou Kazuo Sugimoto Jielin Zhang Yongxiu Liu Yiming Zhang Hao Liang Yinan Jiang Jing Wang Guoxiang Duan Cheng Mei |
author_sort |
Tianyu Zou |
title |
Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1 |
title_short |
Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1 |
title_full |
Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1 |
title_fullStr |
Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1 |
title_full_unstemmed |
Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1 |
title_sort |
geniposide alleviates oxidative stress of mice with depression-like behaviors by upregulating six3os1 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2020-10-01 |
description |
Depression is a major cause of disease burden and severely impairs well-being of patients around the globe. Geniposide (GP) has been revealed to play a significant role in depression treatment. Of note, RNA sequencing of this study identified highly expressed long non-coding RNA Six3os1 in response to GP treatment. Thus, we aim to explore how GP affected chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in mice in vivo and in vitro and the downstream molecular mechanism related to Six3os1. The relationship of Six3os1, miR-511-3p and Fezf1 was evaluated by dual-luciferase reporter gene assay, RIP assay, and RNA pulling down assay. Ectopic expression and knockdown experiments were developed in CUMS-induced mice and neurons with or without GP treatment. In vitro experiments and behavioral tests were conducted to examine alteration of CUMS-triggered oxidative stress following different interferences. The experimental data validated that GP treatment resulted in high expression of Six3os1 and Fezf1 and poor expression of miR-511-3p in CUMS-induced neurons. Six3os1 activated the AKT signaling pathway by upregulating miR-511-3p-targeted Fezf1. Either GP treatment or overexpression of Six3os1 or Fezf1 alleviated depression-like behaviors of CUMS-induced mice. GP treatment, miR-511-3p inhibition or overexpression of Six3os1 or Fezf1 not only reduced oxidative stress in CUMS-induced mice and neurons, but also reduced CUMS-induced neuronal apoptosis. Collectively, GP treatment-mediated Six3os1 upregulation ameliorated oxidative stress of mice with depression-like behaviors via the miR-511-3p/Fezf1/AKT axis. |
topic |
depression geniposide Six3os1 miR-511-3p FEZF1 Akt signaling pathway |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2020.553728/full |
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