抗抑郁药
基因敲除
重性抑郁障碍
安普克
萧条(经济学)
细胞生物学
蛋白激酶A
药理学
内科学
医学
激酶
生物
基因
精神科
生物化学
海马体
认知
经济
宏观经济学
作者
Heyang Zhang,Shuirong Liu,Qiaozhen Qin,Zhenhua Xu,Yannv Qu,Yadi Wang,Jianbo Wang,Zhangzhen Du,Shanshan Yuan,Shunming Hong,Zhilin Chang,Wenyan He,Xinlong Yan,Yiran Lang,Rongyu Tang,Yan Wang,Ling‐Ling Zhu,Xiaoxia Jiang
标识
DOI:10.1002/advs.202204463
摘要
Major depressive disorder (MDD) is a leading cause of disability worldwide. A comprehensive understanding of the molecular mechanisms of this disorder is critical for the therapy of MDD. In this study, it is observed that deubiquitinase Mysm1 is induced in the brain tissues from patients with major depression and from mice with depressive behaviors. The genetic silencing of astrocytic Mysm1 induced an antidepressant-like effect and alleviated the osteoporosis of depressive mice. Furthermore, it is found that Mysm1 knockdown led to increased ATP production and the activation of p53 and AMP-activated protein kinase (AMPK). Pifithrin α (PFT α) and Compound C, antagonists of p53 and AMPK, respectively, repressed ATP production and reversed the antidepressant effect of Mysm1 knockdown. Moreover, the pharmacological inhibition of astrocytic Mysm1 by aspirin relieved depressive-like behaviors in mice. The study reveals, for the first time, the important function of Mysm1 in the brain, highlighting astrocytic Mysm1 as a potential risk factor for depression and as a valuable target for drug discovery to treat depression.
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