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Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?
He, Shen; Shi, Yue; Ye, Jinmei; Yin, Jiahui; Yang, Yufang; Liu, Dan; Shen, Ting; Zeng, Duan; Zhang, Min; Li, Siyuan; Xu, Feikang; Cai, Yiyun; Zhao, Faming; Li, Huafang; Peng, Daihui.
Afiliación
  • He S; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Shi Y; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Ye J; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Yin J; College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • Yang Y; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Liu D; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Shen T; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zeng D; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang M; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Li S; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Xu F; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Cai Y; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhao F; Key Laboratory of Environmental Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. famingzhao@hust.edu.cn.
  • Li H; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. lhlh_5@163.com.
  • Peng D; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. pengdaihui@smhc.org.cn.
Transl Psychiatry ; 13(1): 362, 2023 Nov 25.
Article en En | MEDLINE | ID: mdl-38001115
Astrocytic dysfunction contributes to the molecular pathogenesis of major depressive disorder (MDD). However, the astrocytic subtype that mainly contributes to MDD etiology and whether dysregulated autophagy in astrocytes is associated with MDD remain unknown. Using a single-nucleus RNA sequencing (snRNA-seq) atlas, three astrocyte subtypes were identified in MDD, while C2 State-1Q astrocytes showed aberrant changes in both cell proportion and most differentially expressed genes compared with other subtypes. Moreover, autophagy pathways were commonly inhibited in astrocytes in the prefrontal cortices (PFCs) of patients with MDD, especially in C2 State-1Q astrocytes. Furthermore, by integrating snRNA-seq and bulk transcriptomic data, we found significant reductions in LC3A expression levels in the PFC region of CUMS-induced depressed mice, as well as in postmortem PFC tissues and peripheral blood samples from patients with MDD. These results were further validated by qPCR using whole-blood samples from patients with MDD and healthy controls. Finally, LC3A expression in the whole blood of patients with MDD was negatively associated with the severity of depressive symptoms. Overall, our results underscore autophagy inhibition in PFC astrocytes as a common molecular characteristic in MDD and might reveal a novel potential diagnostic marker LC3A.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Depresivo Mayor Límite: Animals / Humans Idioma: En Revista: Transl Psychiatry Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Depresivo Mayor Límite: Animals / Humans Idioma: En Revista: Transl Psychiatry Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos