ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Microglia-Derived Vitamin D Binding Protein Mediates Synaptic Damage and Induces Depression by Binding to the Neuronal Receptor Megalin.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Receptor-mediated endocytosis by Megalin: Exploring its role in ligand interaction and disease mechanisms.Genes & diseases · 2026Review
- Sex-Specific Hippocampal Phosphoproteomic Features Associated with Stress-Induced Phenotypes in Mice Exposed to Chronic Restraint Stress.Neurochemical research · 2026Article
- Vitamin D as a cellular endocrine system: Tissue-specific microcircuits, immune reprogramming, and metabolic resistance.iScience · 2026Review
- Muribaculum intestinale alleviates depressive-like behaviors by inhibiting Th17 cell differentiation and M1 microglia polarization.Microbiome · 2026Article
- Vitamin D Regulates Olfactory Function via Dual Transcriptional and mTOR-Dependent Translational Control of Synaptic Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The gut microbiota mediates depression-like behaviors in mice with chronic Echinococcus multilocularis infection.NPJ biofilms and microbiomes · 2026Article
- Inflammatory Cytokines as a Shared Pathophysiological Pathway in Depression and Chronic Insomnia: A Narrative Review of Mechanisms and Clinical Implications.Neuropsychiatric disease and treatment · 2026Review
- The regulatory variant rs1950834 confers the risk of depressive disorder by reducing LRFN5 expression.BMC medicine · 2025Article
- Microglia-Derived Vitamin D Binding Protein Mediates Synaptic Damage and Induces Depression by Binding to the Neuronal Receptor Megalin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- HIV-associated depression: a translational framework targeting neuroimmune inflammation and psychosocial stress modulation.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Vitamin D binding protein (VDBP) is a potential biomarker of major depressive disorder (MDD). This study demonstrates for the first time that VDBP is highly expressed in core emotion-related brain regions of mice susceptible to chronic unpredictable mild stress (CUMS). Specifically, the overexpression of microglia (MG)-derived VDBP in the prelimbic leads to depression-like behavior and aggravates CUMS-induced depressive phenotypes in mice, whereas conditional knockout of MG-derived VDBP can reverse both neuronal damage and depression-like behaviors. Mechanistically, the binding of MG-derived VDBP with the neuronal receptor megalin mediates the downstream SRC signaling pathway, leading to neuronal and synaptic damage and depression-like behaviors. These events may be caused by biased activation of inhibitory neurons and excitatory-inhibitory imbalance. Importantly, this study has effectively identified MG-derived VDBP as a pivotal mediator in the interplay between microglia and neurons via its interaction with the neuronal receptor megalin and intricate downstream impacts on neuronal functions, thus offering a promising therapeutic target for MDD.
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