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

Author

Zhang, Heyang, primary, Liu, Shuirong, additional, Qin, Qiaozhen, additional, Xu, Zhenhua, additional, Qu, Yannv, additional, Wang, Yadi, additional, Wang, Jianing, additional, Du, Zhangzhen, additional, Yuan, Shanshan, additional, Hong, Shunming, additional, Chang, Zhilin, additional, He, Wenyan, additional, Yan, Xinlong, additional, Lang, Yiran, additional, Tang, Rongyu, additional, Wang, Yan, additional, Zhu, Lingling, additional, and Jiang, Xiaoxia, additional

Published
2022
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4. Genetic and Pharmacological Inhibition of Astrocytic Mysm1 Alleviates Depressive‐Like Disorders by Promoting ATP Production.

Author

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, and Jiang, Xiaoxia

Subjects
MENTAL depression, GENE silencing, DRUG discovery, AMP-activated protein kinases, P53 protein, PURINERGIC receptors
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 FROM AUTHOR]

Published
2023
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