ArticlePsychopharmacology2019
Chronic stress impairs the aquaporin-4-mediated glymphatic transport through glucocorticoid signaling.
Article in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 85 citations in OpenAlex.
- Glymphatic function in humans: indicators, modulators, and measurement strategies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- The glymphatic system in sleep: a nexus of waste clearance, brain homeostasis, and disease intervention.Molecular psychiatry · 2026Review
- Diffusion Tensor Imaging Along the Perivascular Space in Veterans with Remote Mild Traumatic Brain Injuries.Journal of neurotrauma · 2026Article
- Does Enriched Environment Improve Chronic Immobilization Stress-Induced Cognitive and Behavioral Changes in Adult Male Rats?Cellular and molecular neurobiology · 2026Article
- Adenosine AJournal of neurochemistry · 2026Article
- Ocular Glymphatic System: Its Modulation and Role in Intraocular Tumors.Investigative ophthalmology & visual science · 2026Review
- Association Between Glymphatic Function and White Matter Microstructural Injury in Patients With Cushing's Disease.Brain and behavior · 2026Article
- Cerebellar astrocytic alterations in depression.Translational psychiatry · 2026Article
- Translational assessment of butyrylcholinesterase activity as a diagnostic biomarker for depression using a chemiluminescent probe.Scientific reports · 2026Article
- Aquaporin-4 Dysfunction in Depression: From Pathogenic Mechanisms to Novel Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Glioblastoma pathophysiology: roles of aging driven changes in STAT3 interactions with NF-κB dimer components in the modulation of the mitochondrial melatonergic pathway and night-time inflammation resolution.Exploration of targeted anti-tumor therapy · 2026Review
- Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.Frontiers in neuroscience · 2026Article
- A Meta-Analysis of the Effects of Chronic Stress on the Prefrontal Transcriptome in Animal Models and Convergence with Existing Human Data.bioRxiv : the preprint server for biology · 2025Article
- Across Barriers: Blood-Brain and Gut Barrier Signaling in Psychiatric Disorders.Journal of neurochemistry · 2025Review
- Effect of Cervical Manual Therapy on Sleep Quality: A Scoping Review of Randomized Controlled Trials.Life (Basel, Switzerland) · 2025Review
- The Glymphatic System and Diaphragmatic Dysfunction in Patients with Chronic Obstructive Pulmonary Disease and Chronic Heart Failure: The Importance of Inspiratory Rehabilitation Training.Journal of cardiovascular development and disease · 2025Review
- Stress-induced dysfunction of neurovascular astrocytes in the prefrontal cortex contributes to sex-dependent deficits in cognition and behavior.Molecular psychiatry · 2025Article
- Swept-Source Optical Coherence Tomography Angiography for Retinal Neurovascular Structural Evaluation in a Chronic Unpredictable Mild Stress Rat Model.Translational vision science & technology · 2025Article
- The glymphatic system in Huntington's disease.Journal of Huntington's disease · 2025Review
- When the Stars Misfire: Astrocytic Dysfunctions in Major Depressive Disorder.Neurochemical research · 2025Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe glymphatic system has recently been proposed to function as a brain-wide macroscopic system for the clearance of potentially harmful molecules, such as amyloid beta (e.g., Aβ), from the brain parenchyma. Previous literatures have established that the glymphatic function is dramatically suppressed by aging, traumatic brain injury, and some diseases. However, the effect of chronic stress on the glymphatic function and its underlying mechanism remains largely unknown.
methodsAdult mice were randomly divided into four groups: chronic unpredictable mild stress (CUMS)-treated group, CUMS simultaneously treated with mifepristone (MFP) group, dexamethasone (DEX)-treated group, and control group. Stress response was observed by assessing the change of body weight, plasma corticosterone level, and behavior tests. The level of Aβ42 in cerebral tissue was assessed by ELISA. The glymphatic function was determined by using fluorescence tracer injection. The expression and localization of aquaporin-4 (AQP4) were evaluated by immunohistochemistry and western blot. The transcription level of AQP4 and anchoring molecules was evaluated by real-time PCR.
findingsCompared with control group, CUMS-treated mice exhibited the impairment of global glymphatic function especially in the anterior brain. This change was accompanied by the decreased expression and polarization of AQP4, reduced transcription of AQP4, agrin, laminin, and dystroglycan in the anterior cortex. Similarly, the glucocorticoid receptor (GR) agonist DEX exposure could reduce the glymphatic function and AQP4 expression. Moreover, the GR antagonist MFP treatment could significantly rescue the glymphatic function and reverse the expression and polarization of AQP4 impaired by CUMS.
conclusionChronic stress could impair the AQP4-mediated glymphatic transport in the brain through glucocorticoid signaling. Our results also suggest that GR antagonist could be beneficial to rescue the glymphatic function suppressed by chronic stress.
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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.