Genetic and Pharmacological Inhibition of Astrocytic Mysm1 Alleviates Depressive‐Like Disorders by Promoting ATP Production

• DOI: 10.1002/advs.202204463
• Publication Date: 2022-11-23T02:30:09Z
• Authors: Heyang Zhang; Shuirong Liu; Qiaozhen Qin; Zhenhua Xu; Yannv Qu; Yadi Wang; Jianing Wang; Zhangzhen Du; Shanshan Yuan; Shunming Hong; Zhilin Chang; Wenyan He; Xinlong Yan; Yiran Lang; Rongyu Tang; Yan Wang; Lingling Zhu; Xiaoxia Jiang
• Keywords: ATP; 0301 basic medicine; Mysm1; 03 medical and health sciences; astrocyte; antidepressant effect; aspirin; Science; Q; Research Articles; 3. Good health

Major depressive disorder (MDD) is a leading cause of disability worldwide. A comprehensive understanding the molecular mechanisms this critical for therapy MDD. In study, it observed that deubiquitinase Mysm1 induced in brain tissues from patients with major depression and mice behaviors. The genetic silencing astrocytic an antidepressant-like effect alleviated osteoporosis mice. Furthermore, found knockdown led to increased ATP production activation p53 AMP-activated protein kinase (AMPK). Pifithrin α (PFT α) Compound C, antagonists AMPK, respectively, repressed reversed antidepressant knockdown. Moreover, pharmacological inhibition by aspirin relieved depressive-like behaviors study reveals, first time, important function brain, highlighting as potential risk factor valuable target drug discovery treat depression.