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Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure
Cold stress can induce neuroinflammation in the hippocampal dentate gyrus (DG), but the mechanism underlying neuronal apoptosis induced by cold stress is not well-understood. To address this issue, male and female C57BL/6 mice were exposed to a temperature of 4 °C for 3 h per day for 1 week, and gli...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769965/ https://www.ncbi.nlm.nih.gov/pubmed/31480279 http://dx.doi.org/10.3390/biom9090426 |
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author | Xu, Bin Lang, Li-Min Li, Shi-Ze Guo, Jing-Ru Wang, Jian-Fa Yang, Huan-Min Lian, Shuai |
author_facet | Xu, Bin Lang, Li-Min Li, Shi-Ze Guo, Jing-Ru Wang, Jian-Fa Yang, Huan-Min Lian, Shuai |
author_sort | Xu, Bin |
collection | PubMed |
description | Cold stress can induce neuroinflammation in the hippocampal dentate gyrus (DG), but the mechanism underlying neuronal apoptosis induced by cold stress is not well-understood. To address this issue, male and female C57BL/6 mice were exposed to a temperature of 4 °C for 3 h per day for 1 week, and glial cell activation, neuronal apoptosis, and neuroinflammation were evaluated by western blotting, immunofluorescence, terminal deoxynucleotidyl transferase 2’-deoxyuridine 5’-triphosphate (dUTP) nick end labeling, Nissl staining, and immunohistochemistry. Additionally, BV2 cells were treated with different concentrations of cortisol (CORT) for 3 h to mimic stress and molecular changes were assessed by western blotting, immunofluorescence, and co-immunoprecipitation. We found that excess CORT activated glial cells and increased neuroinflammation in the DG of mice exposed to cold temperatures, which was associated with increased acetylation and nuclear factor-κB signaling. These effects were mediated by the acetylation of lysine 9 of histone 3 and lysine 310 of p65, which resulted in increased mitogen-activated protein kinase phosphorylation, nuclear translocation of p65, microglia activation, and acetylation of high-mobility group box 1. Neuroinflammation was more severe in male compared to female mice. These findings provide new insight into the mechanisms of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia. |
format | Online Article Text |
id | pubmed-6769965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67699652019-10-30 Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure Xu, Bin Lang, Li-Min Li, Shi-Ze Guo, Jing-Ru Wang, Jian-Fa Yang, Huan-Min Lian, Shuai Biomolecules Article Cold stress can induce neuroinflammation in the hippocampal dentate gyrus (DG), but the mechanism underlying neuronal apoptosis induced by cold stress is not well-understood. To address this issue, male and female C57BL/6 mice were exposed to a temperature of 4 °C for 3 h per day for 1 week, and glial cell activation, neuronal apoptosis, and neuroinflammation were evaluated by western blotting, immunofluorescence, terminal deoxynucleotidyl transferase 2’-deoxyuridine 5’-triphosphate (dUTP) nick end labeling, Nissl staining, and immunohistochemistry. Additionally, BV2 cells were treated with different concentrations of cortisol (CORT) for 3 h to mimic stress and molecular changes were assessed by western blotting, immunofluorescence, and co-immunoprecipitation. We found that excess CORT activated glial cells and increased neuroinflammation in the DG of mice exposed to cold temperatures, which was associated with increased acetylation and nuclear factor-κB signaling. These effects were mediated by the acetylation of lysine 9 of histone 3 and lysine 310 of p65, which resulted in increased mitogen-activated protein kinase phosphorylation, nuclear translocation of p65, microglia activation, and acetylation of high-mobility group box 1. Neuroinflammation was more severe in male compared to female mice. These findings provide new insight into the mechanisms of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia. MDPI 2019-08-30 /pmc/articles/PMC6769965/ /pubmed/31480279 http://dx.doi.org/10.3390/biom9090426 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Xu, Bin Lang, Li-Min Li, Shi-Ze Guo, Jing-Ru Wang, Jian-Fa Yang, Huan-Min Lian, Shuai Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure |
title | Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure |
title_full | Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure |
title_fullStr | Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure |
title_full_unstemmed | Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure |
title_short | Microglia Activated by Excess Cortisol Induce HMGB1 Acetylation and Neuroinflammation in the Hippocampal DG Region of Mice Following Cold Exposure |
title_sort | microglia activated by excess cortisol induce hmgb1 acetylation and neuroinflammation in the hippocampal dg region of mice following cold exposure |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769965/ https://www.ncbi.nlm.nih.gov/pubmed/31480279 http://dx.doi.org/10.3390/biom9090426 |
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