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Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice
Long-term treatment with high-dose Interferon-alpha (IFN-α) has resulted in depression in 30–50% of the patients. Paeoniflorin may ameliorate the IFN-α-induced depression; however, the underlying mechanism is less studied. Here, we investigated the prophylactic antidepressant and anti-neuroinflammat...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352399/ https://www.ncbi.nlm.nih.gov/pubmed/28030814 http://dx.doi.org/10.18632/oncotarget.14160 |
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author | Li, Jianwei Huang, Shaohui Huang, Weiliang Wang, Wanshan Wen, Ge Gao, Lei Fu, Xiuqiong Wang, Mengmeng Liang, Weihai Kwan, Hiu Yee Zhao, Xiaoshan Lv, Zhiping |
author_facet | Li, Jianwei Huang, Shaohui Huang, Weiliang Wang, Wanshan Wen, Ge Gao, Lei Fu, Xiuqiong Wang, Mengmeng Liang, Weihai Kwan, Hiu Yee Zhao, Xiaoshan Lv, Zhiping |
author_sort | Li, Jianwei |
collection | PubMed |
description | Long-term treatment with high-dose Interferon-alpha (IFN-α) has resulted in depression in 30–50% of the patients. Paeoniflorin may ameliorate the IFN-α-induced depression; however, the underlying mechanism is less studied. Here, we investigated the prophylactic antidepressant and anti-neuroinflammatory effects of paeoniflorin on the behaviors and specific emotion-related regions of the brain in mice with IFN-α-induced depression. A series of behavior assessments were conducted to identify the depressive state after subcutaneously IFN-α injections and with or without intragastrically paeoniflorin administration in C57BL/6J mice. Levels of many inflammatory-related cytokines in serum, mPFC, vHi and amygdala were determined by cytokine array analysis. Furthermore, microglia and astrocyte activation in these three regions were evaluated by immunohistochemistry. We found that the mice which were subcutaneously injected IFN-α 15×10(6) IU/kg for 4 successive weeks to mimic an IFN-α-induced depression model had distinct inflammatory changes in the amygdala. Interestingly, 4-week 20 mg/kg or 40 mg/kg paeoniflorin pretreatments reversed the depressive-like behaviors and the abnormal inflammatory cytokine levels in the serum, mPFC, vHi and amygdala. These cytokines were not limited to the commonly reported IL-6, IL-1β and TNF-α, but also IL-9, IL-10, IL-12, and MCP-1. Besides, the increased density of microglia in IFN-α-treated mice was reversed by paeoniflorin in these three brain areas. Taken together, our data suggest that paeoniflorin can reverse the long-term, high-dose IFN-α-induced depressive-like behaviors that were associated with local distinct neuroinflammation in the mPFC, vHi and particularly the amygdala. Paeoniflorin might have a preventive therapeutic potential in IFN-α-induced depression. |
format | Online Article Text |
id | pubmed-5352399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53523992017-04-14 Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice Li, Jianwei Huang, Shaohui Huang, Weiliang Wang, Wanshan Wen, Ge Gao, Lei Fu, Xiuqiong Wang, Mengmeng Liang, Weihai Kwan, Hiu Yee Zhao, Xiaoshan Lv, Zhiping Oncotarget Research Paper Long-term treatment with high-dose Interferon-alpha (IFN-α) has resulted in depression in 30–50% of the patients. Paeoniflorin may ameliorate the IFN-α-induced depression; however, the underlying mechanism is less studied. Here, we investigated the prophylactic antidepressant and anti-neuroinflammatory effects of paeoniflorin on the behaviors and specific emotion-related regions of the brain in mice with IFN-α-induced depression. A series of behavior assessments were conducted to identify the depressive state after subcutaneously IFN-α injections and with or without intragastrically paeoniflorin administration in C57BL/6J mice. Levels of many inflammatory-related cytokines in serum, mPFC, vHi and amygdala were determined by cytokine array analysis. Furthermore, microglia and astrocyte activation in these three regions were evaluated by immunohistochemistry. We found that the mice which were subcutaneously injected IFN-α 15×10(6) IU/kg for 4 successive weeks to mimic an IFN-α-induced depression model had distinct inflammatory changes in the amygdala. Interestingly, 4-week 20 mg/kg or 40 mg/kg paeoniflorin pretreatments reversed the depressive-like behaviors and the abnormal inflammatory cytokine levels in the serum, mPFC, vHi and amygdala. These cytokines were not limited to the commonly reported IL-6, IL-1β and TNF-α, but also IL-9, IL-10, IL-12, and MCP-1. Besides, the increased density of microglia in IFN-α-treated mice was reversed by paeoniflorin in these three brain areas. Taken together, our data suggest that paeoniflorin can reverse the long-term, high-dose IFN-α-induced depressive-like behaviors that were associated with local distinct neuroinflammation in the mPFC, vHi and particularly the amygdala. Paeoniflorin might have a preventive therapeutic potential in IFN-α-induced depression. Impact Journals LLC 2016-12-24 /pmc/articles/PMC5352399/ /pubmed/28030814 http://dx.doi.org/10.18632/oncotarget.14160 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Li, Jianwei Huang, Shaohui Huang, Weiliang Wang, Wanshan Wen, Ge Gao, Lei Fu, Xiuqiong Wang, Mengmeng Liang, Weihai Kwan, Hiu Yee Zhao, Xiaoshan Lv, Zhiping Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice |
title | Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice |
title_full | Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice |
title_fullStr | Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice |
title_full_unstemmed | Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice |
title_short | Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice |
title_sort | paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352399/ https://www.ncbi.nlm.nih.gov/pubmed/28030814 http://dx.doi.org/10.18632/oncotarget.14160 |
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