SIRT3
粒体自噬
西妥因1
自噬
氧化应激
锡尔图因
慢性应激
线粒体
下调和上调
生物
加巴能
白藜芦醇
细胞生物学
内分泌学
内科学
神经科学
细胞凋亡
药理学
医学
NAD+激酶
抑制性突触后电位
生物化学
基因
酶
作者
Sidra Tabassum,Afzal Misrani,Huixian Huang,Zaiyong Zhang,Qiao-wei Li,Cheng Long
标识
DOI:10.1007/s12035-023-03395-8
摘要
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/PGC1α/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/PGC1α/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/PGC1α/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.
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