ArticleNature neuroscience2017
Social stress induces neurovascular pathology promoting depression.
Article in Nature neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05541887 (Acute and Chronic Impacts of Muscadine Wine Polyphenols on Cognition, Memory, Mood, and Anxiety in Adults Over 50 Years of Age), which is not on this map. Cited by 590 papers, 4 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.
Acute and Chronic Impacts of Muscadine Wine Polyphenols on Cognition, Memory, Mood, and Anxiety in Adults Over 50 Years of Age
Who cites it
590 citing papers in PubMed, 4 syntheses or guidelines pooled it, 978 citations in OpenAlex.
- Dynamic Cytokine Relationships Across the Blood-Brain Barrier in Humans and Nonhuman Primates-Implications for Psychiatric Illness: A Systematic Review.Biological psychiatry · 2026Pooled it
- TNF-α levels in first-episode, drug-naïve patients with major depressive disorder: a case-control study and meta-analysis.BMC psychiatry · 2026Pooled it
- Meta-analysis of Early Risk Factors Associated with Cerebrovascular Diseases.Current neurovascular research · 2026Pooled it
- Efficacy and Potential Mechanism of Chinese Herbal Formula Chaihu Shugan Powder on Animal Models of Depression: A Systematic Review and Meta-Analysis.CNS neuroscience & therapeutics · 2025Pooled it
- Effects of Dopaminergic Therapy with Levodopa (L-DOPA) on Fear and Anxiety-Related Circuits and Symptoms in Patients with Depression and Higher Inflammation.Brain, behavior, and immunity · 2026Trial
- Maternal gut microbiota mediates prenatal stress-induced fetal blood‒brain barrier dysfunction.Gut microbes · 2026Article
- TranDep: a transcriptomics atlas of depression.Molecular psychiatry · 2026Article
- Role of the Blood-Brain Barrier in the Pathophysiology of Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A Comparative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Chronic social defeat stress induces a hypoglycemic shift and depression-related behaviors, both prevented by antidiabetic drugs.The international journal of neuropsychopharmacology · 2026Article
- Cannabidiol Ameliorates Blood-Brain Barrier Dysfunction and Inhibits Memory Astrocytes Activation in Mice With Sickness-Like Behaviors.CNS neuroscience & therapeutics · 2026Article
- Activation of peripheral muscarinic receptors rescues depressive-like behaviors via gut-brain-axis, involving parasympathetic excitation.Acta pharmacologica Sinica · 2026Article
- Protocol for a randomized, controlled trial of a bioactive dietary polyphenol preparation to promote resilience in healthy individuals.Contemporary clinical trials · 2026Article
- Posttraumatic Stress Disorder Severity-related Accelerated Aging, Hippocampal Volume, and CLDN5 DNA Methylation.Biopsychosocial science and medicine · 2026Article
- Bioactive dietary polyphenols modulate hippocampal inflammasome activation and sex-specific affective behavioral deficits following peripheral Foxp3Research square · 2026Article
- Biomedical Materials and Fabrication Methods for Construction of In Vitro Neurovascular Unit Models.Materials (Basel, Switzerland) · 2026Review
- PMiScience · 2026Review
- Stress and glucocorticoid exposure as a critical environmental risk factor for Alzheimer's disease.Journal of neuroimmunology · 2026Article
- Real-world analysis of depression-related adverse events associated with the adsorbed anthrax vaccine: integrating pharmacovigilance signals, machine learning risk prediction, and transcriptomic mechanisms.Infectious diseases of poverty · 2026Article
- Microglia promote vascular remodeling in a mouse model of chronic stress.Brain, behavior, and immunity · 2026Article
- Liver-derived complement component 3 promotes the susceptibility to stress-induced depression by impairing blood-brain barrier integrity.Molecular psychiatry · 2026Article
530 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 5 institutions in 4 countries.
Funding
Abstract
Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood-brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression.
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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.