ArticleMolecular psychiatry2010
Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole.
Article in Molecular psychiatry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 2 of them syntheses that pooled it.
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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
255 citing papers in PubMed, 2 syntheses or guidelines pooled it, 457 citations in OpenAlex.
- Bibliometric insights into astrocytic roles in depression and treatment.Frontiers in cellular neuroscience · 2024Pooled it
- A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems.Drug discovery today · 2019Pooled it
- Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease.Brain : a journal of neurology · 2021Trial
- Longer-term open-label study of adjunctive riluzole in treatment-resistant depression.Journal of affective disorders · 2019Trial
- Serum and plasma brain-derived neurotrophic factor and response in a randomized controlled trial of riluzole for treatment resistant depression.Journal of affective disorders · 2018Trial
- A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Hippocampal volume and the rapid antidepressant effect of ketamine.Journal of psychopharmacology (Oxford, England) · 2015Trial
- Riluzole likely lacks antidepressant efficacy in ketamine non-responders.Journal of psychiatric research · 2014Trial
- Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.Molecular psychiatry · 2014Trial
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Cumulative mild stress during early life alters prefrontal astrocytic proteins and elevates peripheral S100B in young adult mice.Translational psychiatry · 2026Article
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- The synaptic triad in depression: how stress-related pathways converge on BDNF, NMDA receptor, and MMP-9.Pharmacological reports : PR · 2026Review
- In Vivo Positron Emission Tomography Imaging of Presynaptic Density Reveals Stress-Associated Synaptic Deficits Related to Behavioral and Molecular Alterations in Rats.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2026Article
- Involvement of the central amygdaloid nucleus in the regulation of sex differences in the stress relief response in mice.Biology of sex differences · 2026Article
- Antidepressant-like effects of Ashwagandha (Withania Somnifera) on chronic unpredictable mild stress-induced depression in adolescent rats.Psychopharmacology · 2026Article
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- Disrupted astrocyte-neuron glutamine-glutamate cycling in the medial prefrontal cortex contributes to depression-like behaviors.International journal of biological sciences · 2026Article
- An Overview of Depression Pathogenesis: Prevailing Hypotheses and Associated Neurobiological Underpinnings Primarily Evidenced by Rodent Studies.Depression and anxiety · 2026Review
195 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Growing evidence indicates that glia pathology and amino-acid neurotransmitter system abnormalities contribute to the pathophysiology and possibly the pathogenesis of major depressive disorder. This study investigates changes in glial function occurring in the rat prefrontal cortex (PFC) after chronic unpredictable stress (CUS), a rodent model of depression. Furthermore, we analyzed the effects of riluzole, a Food and Drug Administration-approved drug for the treatment of amyotrophic laterosclerosis, known to modulate glutamate release and facilate glutamate uptake, on CUS-induced glial dysfunction and depressive-like behaviors. We provide the first experimental evidence that chronic stress impairs cortical glial function. Animals exposed to CUS and showing behavioral deficits in sucrose preference and active avoidance exhibited significant decreases in 13C-acetate metabolism reflecting glial cell metabolism, and glial fibrillary associated protein (GFAP) mRNA expression in the PFC. The cellular, metabolic and behavioral alterations induced by CUS were reversed and/or blocked by chronic treatment with the glutamate-modulating drug riluzole. The beneficial effects of riluzole on CUS-induced anhedonia and helplessness demonstrate the antidepressant action of riluzole in rodents. Riluzole treatment also reversed CUS-induced reductions in glial metabolism and GFAP mRNA expression. Our results are consistent with recent open-label clinical trials showing the drug's effect in mood and anxiety disorders. This study provides further validation of hypothesis that glial dysfunction and disrupted amino-acid neurotransmission contribute to the pathophysiology of depression and that modulation of glutamate metabolism, uptake and/or release represent viable targets for antidepressant drug development.
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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.