ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Microglia-Derived Interleukin-6 Triggers Astrocyte Apoptosis in the Hippocampus and Mediates Depression-Like Behavior.
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 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Natural antidepressants in neuroimmunomodulation: molecular mechanisms, action targets, and therapeutic potential.Frontiers in immunology · 2025Pooled it
- CD11c + microglia: From basic research to clinical application.Neural regeneration research · 2026Article
- Both Genetic Manipulation and Acupuncture Alleviate Depressive-Like Behavior Mediated by Astrocytic P2X7 Receptors.MedComm · 2026Article
- Article
- The Gut Microbiota-Astrocyte Axis: New Insights into the Mechanisms of Comorbid Major Depressive Disorder in Type 2 Diabetes Mellitus.Molecular neurobiology · 2026Review
- Continuous OFT-Based Behavioral Phenotyping Reveals Neural Stem Cell-Associated Shifts in Depression-like Mice.Brain sciences · 2026Article
- Microbiota-Driven microglia reprogramming reverses depressive-like behaviors through Peripheral-to-Central immune crosstalk.Molecular psychiatry · 2026Article
- Microglial Activation Is Associated with Hippocampal Synaptic Degeneration and Cognitive Deficits Following Repeated Propofol Exposure.International journal of molecular sciences · 2026Article
- FGF13 alleviates astrocytic apoptosis via JIP2 inhibition in the hippocampus and mitigates depression-like behavior.Journal of neuroinflammation · 2026Article
- Targeting CIRP and IL-6R-mediated microglial inflammation to improve outcomes in intracerebral hemorrhage.Journal of advanced research · 2026Article
- Assessment of glymphatic system function using DTI-ALPS in depressive disorders: a study of its correlation with clinical features and plasma GFAP levels.Quantitative imaging in medicine and surgery · 2026Article
- Neuroimmune programming of childhood trauma: comorbid mechanisms and developmental origins of depression and autoimmune diseases.Journal of neuroinflammation · 2026Review
- Article
- Neurobiology of Anxiety and Depression in CP/CPPS: A Narrative Review of Underlying Mechanisms.Neurology international · 2026Review
- Effect of Interleukin-6 Inhibitors on Rheumatoid Arthritis Pain: Overview of Evidence and Mechanistic Pathways.Pharmacology research & perspectives · 2026Review
- Acod1/itaconate axis controls anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice.PLoS neglected tropical diseases · 2026Article
- Low-Intensity Pulsed Ultrasound Alleviation of LPS-Induced Depression-Like Behavior via Microglial P2X4R Inhibition and BDNF/TrkB Pathway Activation.CNS neuroscience & therapeutics · 2026Article
- The tango of immune and neural cells: orchestrating neuroinflammation mediated brain disorders.Frontiers in immunology · 2026Review
- Abuse Potential and Neurotoxic Effects of the Synthetic Cannabinoid 4F-ABUTINACA Self-Administration in Adult Male Rats.Addiction biology · 2026Article
- DPP-4 inhibitors in drug-resistant epilepsy: a hypothesized mechanism via the gut microbiota-short-chain fatty acids-glucagon-like peptide-1 axis.Frontiers in immunology · 2026Review
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11 authors.
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Abstract
In patients with major depressive disorder (MDD) and animal models of depression, key pathological hallmarks include activation of microglia as well as atrophy and loss of astrocytes. Under certain pathological conditions, microglia can inflict damage to neurons and astrocytes. However, the precise mechanisms underlying how activated microglia induced astrocyte atrophy and loss remain enigmatic. In this study, a depression model induced by chronic social defeat stress (CSDS) is utilized. The results show that CSDS induces significant anxiety- and depression-like behaviors, along with notable astrocyte atrophy and apoptosis, microglial activation, and elevated levels of microglial interleukin-6 (IL-6). Subsequent studies demonstrate that IL-6 released from activated microglia promotes astrocyte apoptosis. Furthermore, the knockdown of the P2X7 receptor (P2X7R) in microglia, which is implicated in the stress response, reduces stress-induced microglial activation, IL-6 release, and astrocyte apoptosis. Direct inhibition of microglia by minocycline corroborates these effects. The selective knockdown of IL-6 in microglia and IL-6 receptors in astrocytes effectively mitigates depression-like behaviors and reduces astrocyte atrophy. This study identifies microglial IL-6 as a key factor that contributes to astrocyte apoptosis and depressive symptoms. Consequently, the IL-6/IL-6R pathway has emerged as a promising target for the treatment of depression.
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