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Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway
BACKGROUND: In Alzheimer’s disease, growing evidence has shown that uncontrolled glial activation and neuroinflammation may contribute independently to neurodegeneration. Antiinflammatory strategies might provide benefits for this devastating disease. The aims of the present study are to address the...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360237/ https://www.ncbi.nlm.nih.gov/pubmed/25618401 http://dx.doi.org/10.1093/ijnp/pyu022 |
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author | Zhu, Shenghua Shi, Ruoyang Li, Victor Wang, Junhui Zhang, Ruiguo Tempier, Adrien He, Jue Kong, Jiming Wang, Jun-Feng Li, Xin-Min |
author_facet | Zhu, Shenghua Shi, Ruoyang Li, Victor Wang, Junhui Zhang, Ruiguo Tempier, Adrien He, Jue Kong, Jiming Wang, Jun-Feng Li, Xin-Min |
author_sort | Zhu, Shenghua |
collection | PubMed |
description | BACKGROUND: In Alzheimer’s disease, growing evidence has shown that uncontrolled glial activation and neuroinflammation may contribute independently to neurodegeneration. Antiinflammatory strategies might provide benefits for this devastating disease. The aims of the present study are to address the issue of whether glial activation and proinflammatory cytokine increases could be modulated by quetiapine in vivo and in vitro and to explore the underlying mechanism. METHODS: Four-month–old amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic and nontransgenic mice were treated with quetiapine (5mg/kg/d) in drinking water for 8 months. Animal behaviors, total Aβ levels, and glial activation were evaluated by behavioral tests, enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot accordingly. Inflammatory cytokines and the nuclear factor kappa B pathway were analyzed in vivo and in vitro. RESULTS: Quetiapine improves behavioral performance, marginally affects total Aβ(40) and Aβ(42) levels, attenuates glial activation, and reduces proinflammatory cytokines in APP/PS1 mice. Quetiapine suppresses Aβ(1-42)-induced activation of primary microglia by decresing proinflammatory cytokines. Quetiapine inhibits the activation of nuclear factor kappa B p65 pathway in both transgenic mice and primary microglia stimulated by Aβ(1–42). CONCLUSIONS: The antiinflammatory effects of quetiapine in Alzheimer’s disease may be involved in the nuclear factor kappa B pathway. Quetiapine may be an efficacious and promising treatment for Alzheimer’s disease targeting on neuroinflammation. |
format | Online Article Text |
id | pubmed-4360237 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43602372015-09-01 Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway Zhu, Shenghua Shi, Ruoyang Li, Victor Wang, Junhui Zhang, Ruiguo Tempier, Adrien He, Jue Kong, Jiming Wang, Jun-Feng Li, Xin-Min Int J Neuropsychopharmacol Research Article BACKGROUND: In Alzheimer’s disease, growing evidence has shown that uncontrolled glial activation and neuroinflammation may contribute independently to neurodegeneration. Antiinflammatory strategies might provide benefits for this devastating disease. The aims of the present study are to address the issue of whether glial activation and proinflammatory cytokine increases could be modulated by quetiapine in vivo and in vitro and to explore the underlying mechanism. METHODS: Four-month–old amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic and nontransgenic mice were treated with quetiapine (5mg/kg/d) in drinking water for 8 months. Animal behaviors, total Aβ levels, and glial activation were evaluated by behavioral tests, enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot accordingly. Inflammatory cytokines and the nuclear factor kappa B pathway were analyzed in vivo and in vitro. RESULTS: Quetiapine improves behavioral performance, marginally affects total Aβ(40) and Aβ(42) levels, attenuates glial activation, and reduces proinflammatory cytokines in APP/PS1 mice. Quetiapine suppresses Aβ(1-42)-induced activation of primary microglia by decresing proinflammatory cytokines. Quetiapine inhibits the activation of nuclear factor kappa B p65 pathway in both transgenic mice and primary microglia stimulated by Aβ(1–42). CONCLUSIONS: The antiinflammatory effects of quetiapine in Alzheimer’s disease may be involved in the nuclear factor kappa B pathway. Quetiapine may be an efficacious and promising treatment for Alzheimer’s disease targeting on neuroinflammation. Oxford University Press 2015-01-24 /pmc/articles/PMC4360237/ /pubmed/25618401 http://dx.doi.org/10.1093/ijnp/pyu022 Text en © The Author 2015. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Article Zhu, Shenghua Shi, Ruoyang Li, Victor Wang, Junhui Zhang, Ruiguo Tempier, Adrien He, Jue Kong, Jiming Wang, Jun-Feng Li, Xin-Min Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway |
title | Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway |
title_full | Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway |
title_fullStr | Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway |
title_full_unstemmed | Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway |
title_short | Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor-κB Pathway |
title_sort | quetiapine attenuates glial activation and proinflammatory cytokines in app/ps1 transgenic mice via inhibition of nuclear factor-κb pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360237/ https://www.ncbi.nlm.nih.gov/pubmed/25618401 http://dx.doi.org/10.1093/ijnp/pyu022 |
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