ArticleJournal of advanced research2024
HMGB1/STAT3/p65 axis drives microglial activation and autophagy exert a crucial role in chronic Stress-Induced major depressive disorder.
Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Natural antidepressants in neuroimmunomodulation: molecular mechanisms, action targets, and therapeutic potential.Frontiers in immunology · 2025Pooled it
- Immune-related biomarkers for major depressive disorder identified via integrated bioinformatics and machine learning.European journal of psychotraumatology · 2026Review
- GATA3 drives chronic stress-induced depressive-like behaviors by reducing hippocampal CA3 pyramidal neuronal activity in male mice.Acta pharmacologica Sinica · 2026Article
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- Curculigoside Alleviates CSDS-induced Depressive-like Behavior by Modulating Pyramidal Neuron Excitability and Synaptic Transmission.Neuromolecular medicine · 2026Article
- Consistent decline of acetylcholine in microbiota-gut-brain axis mediates antibiotic-induced anxiety via regulating hippocampus microglial activation.Molecular psychiatry · 2026Article
- Inflachromene Blocks Neuronal HMGB1 Translocation to Mitigate Hippocampal TLR4-NF-κB-Mediated Neuroinflammation and Depression-Like Behavior After Spinal Cord Injury.Molecular neurobiology · 2026Article
- CircADAM9 activates autophagy via miR-302b-3p/ULK1 axis to improve depressive-like behaviors.Biology direct · 2026Article
- The gut microbiota mediates depression-like behaviors in mice with chronic Echinococcus multilocularis infection.NPJ biofilms and microbiomes · 2026Article
- Gut metabolite indole-3-acetic acid aggravates neuropsychiatric lupus via the AHR/STAT3 pathway in microglia.Communications biology · 2026Article
- Pharmacological mechanisms of natural products with antidepressant effects: A focus on the programmed cell death regulation.Journal of pharmaceutical analysis · 2026Review
- Targeting Programmed Cell Death in Depression: A Review of Traditional Chinese Medicine Interventions Based on Preclinical Evidence.Neuropsychiatric disease and treatment · 2026Review
- Targeting the cGAS-STING Pathway: Modulating Inflammation, Oxidative Stress, and Autophagy for Novel Depression Therapies.Current neuropharmacology · 2026Review
- Review
- Progress and challenges in exploring the pathogenesis of depressive disorders via RNA sequencing.Frontiers in genetics · 2026Review
- Interactions between upper respiratory microbiota and psychological distress in pulmonary nodule patients: a retrospective nested case-control study based on machine learning and exploratory mediation analysis.International journal of surgery (London, England) · 2025Article
- Neonatal bone marrow interstitial fluid supports expansion and osteogenic ability of human bone marrow mesenchymal stromal cells.Bone research · 2025Article
- [Role and Mechanism of High Mobility Group Box 1 in Mediating Depression-Like Behaviors in Mice via Regulation of the 5-Hydroxytryptamine Receptor 7 Signaling Pathway].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Chronic administration of isotretinoin induces depressive- and anxiety-like behaviors by altering the neuroactive ligand-receptor interaction pathway in adolescent mice.Translational psychiatry · 2025Article
- Esketamine alleviates depressive-like behavior in mice via modulation of the microbiota-gut-brain axis and amino acid metabolism.BMC microbiology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionNeuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown.
objectivesHere, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro.
methodsBioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD.
resultsThe differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes.
conclusionOur study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.