Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 03760, Republic of Korea.
Commun Biol. 2020 Jun 5;3(1):292. doi: 10.1038/s42003-020-1010-5.
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.
脑老化伴随着边缘系统的细胞和分子变化。与年龄相关的变化可能会影响情绪和应对压力的能力，但潜在的机制仍不清楚。在这里，我们发现老年（18 个月大）小鼠的海马体中 NADPH 氧化酶和氧化应激上调，这与年轻（2 个月大）小鼠在慢性应激下的变化相吻合。缺乏 NADPH 氧化酶关键亚基 p47phox 的老年小鼠不会出现氧化应激增加的情况。在弱应激下，老年小鼠会表现出类似抑郁的行为，而这种行为不会在年轻小鼠中产生。老年小鼠的表观遗传因子 SUV39H1 及其上游调节因子 p-AMPK 的表达减少，以及 Ppp2ca 在海马体中的表达增加，这些变化发生在暴露于慢性应激的年轻小鼠中。SUV39H1 介导应激和衰老诱导的 p47phox 和氧化应激的持续上调。这些结果表明，衰老通过在海马体中上调 NADPH 氧化酶增加了对压力的敏感性。
