The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior

The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior

Abstract Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a...

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Autores principales: Yufeng Jia, Xiao Zhuang, Yi Zhang, Ming Zhao, Nuo Chen, Wen Li, Faliang Zhu, Chun Guo, Yan Li, Qun Wang, Yuan Li, Lining Zhang
Formato: article
Lenguaje:EN
Publicado: Nature Publishing Group 2021
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Cytology
QH573-671
Acceso en línea:https://doaj.org/article/5cf2ede67af44817b7d4b847604a0517
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spelling oai:doaj.org-article:5cf2ede67af44817b7d4b847604a05172021-11-14T12:07:00ZThe brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior10.1038/s41419-021-04361-92041-4889https://doaj.org/article/5cf2ede67af44817b7d4b847604a05172021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04361-9https://doaj.org/toc/2041-4889Abstract Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.Yufeng JiaXiao ZhuangYi ZhangMing ZhaoNuo ChenWen LiFaliang ZhuChun GuoYan LiQun WangYuan LiLining ZhangNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Cytology
QH573-671
spellingShingle Cytology
QH573-671
Yufeng Jia
Xiao Zhuang
Yi Zhang
Ming Zhao
Nuo Chen
Wen Li
Faliang Zhu
Chun Guo
Yan Li
Qun Wang
Yuan Li
Lining Zhang
The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior
description Abstract Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.
format article
author Yufeng Jia
Xiao Zhuang
Yi Zhang
Ming Zhao
Nuo Chen
Wen Li
Faliang Zhu
Chun Guo
Yan Li
Qun Wang
Yuan Li
Lining Zhang
author_facet Yufeng Jia
Xiao Zhuang
Yi Zhang
Ming Zhao
Nuo Chen
Wen Li
Faliang Zhu
Chun Guo
Yan Li
Qun Wang
Yuan Li
Lining Zhang
author_sort Yufeng Jia
title The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior
title_short The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior
title_full The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior
title_fullStr The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior
title_full_unstemmed The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior
title_sort brain targeted delivery of programmed cell death 4 specific sirna protects mice from crs-induced depressive behavior
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/5cf2ede67af44817b7d4b847604a0517
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