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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2021
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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) |
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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 |
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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 |
work_keys_str_mv |
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