Genetic and Pharmacological Inhibition of Astrocytic Mysm1 Alleviates Depressive‐Like Disorders by Promoting ATP Production. Issue 1 (22nd November 2022)

• Record Type: Journal Article
• Authors: Zhang, Heyang; Liu, Shuirong; Qin, Qiaozhen; Xu, Zhenhua; Qu, Yannv; Wang, Yadi; Wang, Jianing; Du, Zhangzhen; Yuan, Shanshan; Hong, Shunming; Chang, Zhilin; He, Wenyan; Yan, Xinlong; Lang, Yiran; Tang, Rongyu; Wang, Yan; Zhu, Lingling; Jiang, Xiaoxia
• Is Part Of: Advanced science. Volume 10:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-22
• Subjects: antidepressant effect -- aspirin -- astrocyte -- ATP -- Mysm1; Science -- Periodicals; 505
• DOI: 10.1002/advs.202204463
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : Deubiquitinase Mysm1 is induced in the brain tissues from patients with major depression and from mice with depressive behaviors. Genetic and pharmacological inhibition of Mysm1 lead to increased ATP production and activation of p53 and AMP‐activated protein kinase (AMPK) and then relieved depressive‐like behaviors in mice. This study reveals the important function of Mysm1 in the brain.