ArticleTranslational psychiatry2023
Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?
Article in Translational psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- The Gut Microbiota-Astrocyte Axis: New Insights into the Mechanisms of Comorbid Major Depressive Disorder in Type 2 Diabetes Mellitus.Molecular neurobiology · 2026Review
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Review
- Astrocytes: Unveiling their role in the molecular mechanism of natural antidepressants.Journal of pharmaceutical analysis · 2026Review
- Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-Nucleus RNA Sequencing Reveals Mid-Gestational Neurodevelopment Features in the Superior Temporal Plane from Fetuses with Nonsyndromic Cleft Lip and Palate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mental health and gut-brain crosstalk: implications for depression and Alzheimer's disease.Neuroscience applied · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- SDFA: a standardized decomposition format and toolkit for efficient analysis of structural variants in large-scale population genomic studies.Genome biology · 2025Article
- Autophagy Modulation by Antidepressants: Mechanisms and Implications.Neurochemical research · 2025Review
- A depression-associated protein FKBP5 functions in autophagy initiation through scaffolding the VPS34 complex.Molecular neurobiology · 2025Article
- Review
- Prefrontal cortex astrocytes in major depressive disorder: exploring pathogenic mechanisms and potential therapeutic targets.Journal of molecular medicine (Berlin, Germany) · 2024Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
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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