4.6 Article

Resveratrol Attenuates Chronic Unpredictable Mild Stress-Induced Alterations in the SIRT1/PGC1α/SIRT3 Pathway and Associated Mitochondrial Dysfunction in Mice

期刊

MOLECULAR NEUROBIOLOGY
卷 60, 期 9, 页码 5102-5116

出版社

SPRINGER
DOI: 10.1007/s12035-023-03395-8

关键词

Chronic stress; SIRT1; Mitochondrial dysfunction; GABAergic; Anxiety-like behavior; Depressive-like behavior

向作者/读者索取更多资源

Environmental challenges, specifically chronic stress, have a negative impact on the SIRT1/PGC1 alpha/SIRT3 pathway and associated signaling, leading to impaired mitochondrial function and morphology, reduced numbers of interneurons, and increased oxidative stress. However, activation of SIRT1 by resveratrol (RSV) can ameliorate these effects and improve mitochondrial function, GABAergic mechanisms, autophagy, and apoptosis. Furthermore, RSV treatment can rescue anxiety-like and depressive-like behaviors induced by chronic stress.
Environmental challenges, specifically chronic stress, have long been associated with neuropsychiatric disorders, including anxiety and depression. Sirtuin-1 (SIRT1) is a NAD(+)-dependent deacetylase that is widely distributed in the cortex and is involved in stress responses and neuropsychiatric disorders. Nevertheless, how chronic stress modulates the SIRT1 pathway and associated signaling remains unclear. In this study, we first explored the impact of chronic unpredictable mild stress (CUMS) on the SIRT1/PGC1 alpha/SIRT3 pathway, on GABAergic mechanisms, and on mitophagy, autophagy and apoptosis in mice. We also asked whether activation of SIRT1 by resveratrol (RSV) can attenuate CUMS-induced molecular and behavioral alterations. Two-month-old C57/BL6J mice were subjected to three weeks of CUMS and one week of RSV treatment (30 mg/kg; i.p.) during the third week of CUMS. CUMS caused downregulation of the SIRT1/PGC1 alpha/SIRT3 pathway leading to impaired mitochondrial morphology and function. CUMS also resulted in a reduction in numbers of parvalbumin-positive interneurons and increased oxidative stress leading to reduced expression of autophagy- and mitophagy-related proteins. Strikingly, activation of SIRT1 by RSV ameliorated expression of SIRT1/PGC1 alpha/SIRT3, and also improved mitochondrial function, GABAergic mechanisms, mitophagy, autophagy and apoptosis. RSV also rescued CUMS-induced anxiety-like and depressive-like behavior in mice. Our results raise the compelling possibility that RSV treatment might be a viable therapeutic method of blocking stress-induced behavioral alterations.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据