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

Jung Eun Lee, Hye Jin Kwon, Juli Choi, Ji Seon Seo, Pyung Lim Han

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Article number292
JournalCommunications Biology
Volume3
Issue number1
DOIs
StatePublished - 1 Dec 2020

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