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Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice

Brain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippoc...

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Autores principales: Lee, Jung-Eun, Kwon, Hye-Jin, Choi, Juli, Seo, Ji-Seon, Han, Pyung-Lim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275057/
https://www.ncbi.nlm.nih.gov/pubmed/32504071
http://dx.doi.org/10.1038/s42003-020-1010-5
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author Lee, Jung-Eun
Kwon, Hye-Jin
Choi, Juli
Seo, Ji-Seon
Han, Pyung-Lim
author_facet Lee, Jung-Eun
Kwon, Hye-Jin
Choi, Juli
Seo, Ji-Seon
Han, Pyung-Lim
author_sort Lee, Jung-Eun
collection PubMed
description Brain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippocampus, which mirrors the changes in young (2-month-old) mice subjected to chronic stress. Aged mice that lack p47phox, a key subunit of NADPH oxidase, do not show increased oxidative stress. Aged mice exhibit depression-like behavior following weak stress that does not produce depressive behavior in young mice. Aged mice have reduced expression of the epigenetic factor SUV39H1 and its upstream regulator p-AMPK, and increased expression of Ppp2ca in the hippocampus—changes that occur in young mice exposed to chronic stress. SUV39H1 mediates stress- and aging-induced sustained upregulation of p47phox and oxidative stress. These results suggest that aging increases susceptibility to stress by upregulating NADPH oxidase in the hippocampus.
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spelling pubmed-72750572020-06-16 Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice Lee, Jung-Eun Kwon, Hye-Jin Choi, Juli Seo, Ji-Seon Han, Pyung-Lim Commun Biol Article Brain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippocampus, which mirrors the changes in young (2-month-old) mice subjected to chronic stress. Aged mice that lack p47phox, a key subunit of NADPH oxidase, do not show increased oxidative stress. Aged mice exhibit depression-like behavior following weak stress that does not produce depressive behavior in young mice. Aged mice have reduced expression of the epigenetic factor SUV39H1 and its upstream regulator p-AMPK, and increased expression of Ppp2ca in the hippocampus—changes that occur in young mice exposed to chronic stress. SUV39H1 mediates stress- and aging-induced sustained upregulation of p47phox and oxidative stress. These results suggest that aging increases susceptibility to stress by upregulating NADPH oxidase in the hippocampus. Nature Publishing Group UK 2020-06-05 /pmc/articles/PMC7275057/ /pubmed/32504071 http://dx.doi.org/10.1038/s42003-020-1010-5 Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lee, Jung-Eun
Kwon, Hye-Jin
Choi, Juli
Seo, Ji-Seon
Han, Pyung-Lim
Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice
title Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice
title_full Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice
title_fullStr Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice
title_full_unstemmed Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice
title_short Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice
title_sort aging increases vulnerability to stress-induced depression via upregulation of nadph oxidase in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275057/
https://www.ncbi.nlm.nih.gov/pubmed/32504071
http://dx.doi.org/10.1038/s42003-020-1010-5
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