ArticleBiological psychiatry2018
Persistent Increase in Microglial RAGE Contributes to Chronic Stress-Induced Priming of Depressive-like Behavior.
Article in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
101 citing papers in PubMed, 3 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- Depression as a predictor of postoperative delirium after cardiac surgery: a systematic review and meta-analysis.Interactive cardiovascular and thoracic surgery · 2021Pooled it
- The assessment of stress, depression, and inflammation as a collective risk factor for periodontal diseases: a systematic review.Clinical oral investigations · 2020Pooled it
- HMGB1 involved in stress-induced depression and its neuroinflammatory priming role: a systematic review.General psychiatry · 2019Pooled it
- Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration.Neural regeneration research · 2026Article
- Sex and stress paradigm influence behavioural, neuroimmune, and microbiome responses in pubertal CD-1 mice.Brain, behavior, & immunity - health · 2026Article
- Dysregulation of the TLR4/MyD88/NF-κB Signaling Pathway and Pro-Inflammatory Cytokines in First-Episode Major Depressive Disorder: A Cross-Sectional Case-Control Study.Immunity, inflammation and disease · 2026Article
- NLRP3-mediated trained immunity of microglia is involved in the recurrence-like episode of depressive disorders.Molecular psychiatry · 2026Article
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- Chamomile Modulates Glucose Metabolism and Neuro-inflammation to Alleviate Stress-Induced Depression in Mice.Molecular neurobiology · 2025Article
- Recent Change in Anhedonia, Major Depression and Low-Grade Inflammation: Dangerous Liaisons? A Study Based on a Cohort Referred for Polysomnography.Medicina (Kaunas, Lithuania) · 2025Article
- Persistent pain signaling and stress response in a mouse model of inflammatory low back pain.Pain reports · 2025Article
- Review
- Sensory neurostimulation promotes stress resilience with frequency-specificity.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Effect and Mechanism of Liraglutide in Treating Depression Based on Network Pharmacology and Experimental Analysis.Journal of cellular and molecular medicine · 2025Article
- The Receptor for Advanced Glycation End-products in the Mouse Anterior Cingulate Cortex is Involved in Neuron‒Astrocyte Coupling in Chronic Inflammatory Pain and Anxiety Comorbidity.Molecular neurobiology · 2025Article
- Stress-Induced Sleep Dysregulation: The Roles of Astrocytes and Microglia in Neurodegenerative and Psychiatric Disorders.Biomedicines · 2025Review
- Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice.Neurobiology of stress · 2025Article
- Schaftoside Reduces Depression- and Anxiogenic-like Behaviors in Mice Depression Models.Brain sciences · 2025Article
- The Ambiguous Role of HMGB1 Across the Hallmarks of Aging: A Narrative Review.Clinical interventions in aging · 2025Review
- The Biological Changes of Synaptic Plasticity in the Pathological Process of Sepsis-associated Encephalopathy.Current neuropharmacology · 2025Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChronic stress-induced inflammatory responses occur in part via danger-associated molecular pattern (DAMP) molecules, such as high mobility group box 1 protein (HMGB1), but the receptor(s) underlying DAMP signaling have not been identified.
methodsMicroglia morphology and DAMP signaling in enriched rat hippocampal microglia were examined during the development and expression of chronic unpredictable stress (CUS)-induced behavioral deficits, including long-term, persistent changes after CUS.
resultsThe results show that CUS promotes significant morphological changes and causes robust upregulation of HMGB1 messenger RNA in enriched hippocampal microglia, an effect that persists for up to 6 weeks after CUS exposure. This coincides with robust and persistent upregulation of receptor for advanced glycation end products (RAGE) messenger RNA, but not toll-like receptor 4 in hippocampal microglia. CUS also increased surface expression of RAGE protein on hippocampal microglia as determined by flow cytometry and returned to basal levels 5 weeks after CUS. Importantly, exposure to short-term stress was sufficient to increase RAGE surface expression as well as anhedonic behavior, reflecting a primed state that results from a persistent increase in RAGE messenger RNA expression. Further evidence for DAMP signaling in behavioral responses is provided by evidence that HMGB1 infusion into the hippocampus was sufficient to cause anhedonic behavior and by evidence that RAGE knockout mice were resilient to stress-induced anhedonia.
conclusionsTogether, the results provide evidence of persistent microglial HMGB1-RAGE expression that increases vulnerability to depressive-like behaviors long after chronic stress exposure.
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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.