ReviewFrontiers in cellular neuroscience2015
Depression as a Glial-Based Synaptic Dysfunction.
Review in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- Pooled it
- Meta-analysis of expression and methylation signatures indicates a stress-related epigenetic mechanism in multiple neuropsychiatric disorders.Translational psychiatry · 2019Pooled it
- Comparison Between Viscous Teardrops and Saline Solution to Fill Orthokeratology Contact Lenses Before Overnight Wear.Eye & contact lens · 2018Trial
- The Monoamine-Glutamate Continuum of Depression: A Neurobiological Framework for Precision Psychiatry.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Exploring the potential of polyphenols in major depression: from molecular function to clinical therapy.Frontiers in nutrition · 2026Review
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- "Stand by me": astrocyte-microglia crosstalk in central nervous system development, homeostasis, injury, and disease.Frontiers in network physiology · 2026Review
- Cellular heterogeneity and multicellular mechanisms in the pathogenesis of late-life depression: insights from single-cell and spatial multi-omics.Frontiers in immunology · 2026Review
- Multidimensional Data-Driven Mechanistic Insights into Anle Tablets for Depression Treatment through Molecular Docking and Dynamics.Current pharmaceutical design · 2026Article
- Research Progress of Functionalized Drug Delivery Nanosystems in Regulating Depression.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Maladaptive Neuroplasticity Under Stress: Insights into Neuronal and Synaptic Changes in the Prefrontal Cortex.Molecular neurobiology · 2025Review
- Helicobacter hepaticus CdtB promoted brain impairment in BALB/c mice via gut-brain axis.Gut pathogens · 2025Article
- Adaptations in Mitochondrial Function Induced by Exercise: A Therapeutic Route for Treatment-Resistant Depression.International journal of molecular sciences · 2025Review
- Autophagy Modulation by Antidepressants: Mechanisms and Implications.Neurochemical research · 2025Review
- Combination method of macroscopic imaging with MRI and microscopic imaging with super resolution microscopy for brain microstructure analysis.Anatomical science international · 2025Article
- Ferroptosis: a new target for depression prevention and treatment.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Review
- A vascular endothelial cell, neuron, and microglia tri-culture model to study hypertension-related depression.Frontiers in cellular neuroscience · 2025Article
- Effects of all-trans retinoic acid on glutamate receptor expression and dendritic spine density in the hypothalamus of rats.Frontiers in neuroscience · 2025Article
- The central role of microglia in major depressive disorder and its potential as a therapeutic target.Frontiers in behavioral neuroscience · 2025Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the "quad-partite" synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia "activation" in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain-derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication-such as the purinergic neuromodulation system operated by adenosine 5'-triphosphate (ATP) and adenosine-emerge as promising candidates to "re-normalize" synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage 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.