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Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them

BACKGROUND: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects....

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Autores principales: Al Omran, Alzahra J., Shao, Amy S., Watanabe, Saki, Zhang, Zeyu, Zhang, Jifeng, Xue, Chen, Watanabe, Junji, Davies, Daryl L., Shao, Xuesi M., Liang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724741/
https://www.ncbi.nlm.nih.gov/pubmed/34983568
http://dx.doi.org/10.1186/s12974-021-02368-9
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author Al Omran, Alzahra J.
Shao, Amy S.
Watanabe, Saki
Zhang, Zeyu
Zhang, Jifeng
Xue, Chen
Watanabe, Junji
Davies, Daryl L.
Shao, Xuesi M.
Liang, Jing
author_facet Al Omran, Alzahra J.
Shao, Amy S.
Watanabe, Saki
Zhang, Zeyu
Zhang, Jifeng
Xue, Chen
Watanabe, Junji
Davies, Daryl L.
Shao, Xuesi M.
Liang, Jing
author_sort Al Omran, Alzahra J.
collection PubMed
description BACKGROUND: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. METHODS: Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. RESULTS: Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes. CONCLUSION: The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02368-9.
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spelling pubmed-87247412022-01-04 Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them Al Omran, Alzahra J. Shao, Amy S. Watanabe, Saki Zhang, Zeyu Zhang, Jifeng Xue, Chen Watanabe, Junji Davies, Daryl L. Shao, Xuesi M. Liang, Jing J Neuroinflammation Research BACKGROUND: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. METHODS: Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. RESULTS: Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes. CONCLUSION: The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02368-9. BioMed Central 2022-01-04 /pmc/articles/PMC8724741/ /pubmed/34983568 http://dx.doi.org/10.1186/s12974-021-02368-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Al Omran, Alzahra J.
Shao, Amy S.
Watanabe, Saki
Zhang, Zeyu
Zhang, Jifeng
Xue, Chen
Watanabe, Junji
Davies, Daryl L.
Shao, Xuesi M.
Liang, Jing
Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
title Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
title_full Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
title_fullStr Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
title_full_unstemmed Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
title_short Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
title_sort social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724741/
https://www.ncbi.nlm.nih.gov/pubmed/34983568
http://dx.doi.org/10.1186/s12974-021-02368-9
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