ArticlePsychopharmacology2016
Regulation of glutamate transporter 1 via BDNF-TrkB signaling plays a role in the anti-apoptotic and antidepressant effects of ketamine in chronic unpredictable stress model of depression.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity.Frontiers in psychiatry · 2022Pooled it
- The Gut Microbiota-Astrocyte Axis: New Insights into the Mechanisms of Comorbid Major Depressive Disorder in Type 2 Diabetes Mellitus.Molecular neurobiology · 2026Review
- Low Dose Ketamine Preconditions Astrocyte Mitochondria to Achieve Antidepressant Efficacy via Adenosine, Humanin, and Melatonin Upregulation and Efflux.Alpha psychiatry · 2026Article
- Cerebroprotective potential of ceftriaxone against cadmium chloride-induced cerebral inflammatory changes and oxidative insult.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- An Overview of Depression Pathogenesis: Prevailing Hypotheses and Associated Neurobiological Underpinnings Primarily Evidenced by Rodent Studies.Depression and anxiety · 2026Review
- Lurasidone ameliorates doxorubicin-induced chemobrain in male Wistar rats: involvement of the hippocampal and prefrontal cortex CREB/BDNF/Glt-1 axis and glutamate homeostasis.Frontiers in pharmacology · 2026Article
- Do immune system and microbiome-gut-brain axis interactions associate with major depressive disorder?Journal of translational medicine · 2025Review
- Biomimetic ferritin nanocages for synergistic co-delivery of metformin and rapamycin restore neurodevelopmental homeostasis in autism spectrum disorders.Journal of nanobiotechnology · 2025Article
- Are "mystical experiences" essential for antidepressant actions of ketamine and the classic psychedelics?European archives of psychiatry and clinical neuroscience · 2025Review
- Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways.Science advances · 2025Article
- Effects of Subanesthetic Intravenous Ketamine Infusion on Stress Hormones and Synaptic Density in Rats with Mild Closed-Head Injury.Biomedicines · 2025Article
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook.Frontiers in psychiatry · 2025Review
- Ketamine Reduces Avoidance Responses During Re-Exposition to Aversive Stimulus: Comparison Between (Brain sciences · 2024Article
- Beyond NMDA Receptors: A Narrative Review of Ketamine's Rapid and Multifaceted Mechanisms in Depression Treatment.International journal of molecular sciences · 2024Review
- Ketamine attenuates kidney damage and depression-like behaviors in mice with cisplatin-induced acute kidney injury.Translational psychiatry · 2024Article
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions.Journal of anesthesia and translational medicine · 2024Review
- Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target.International journal of molecular sciences · 2024Review
- Effects of Mild Closed-Head Injury and Subanesthetic Ketamine Infusion on Microglia, Axonal Injury, and Synaptic Density in Sprague-Dawley Rats.International journal of molecular sciences · 2024Article
- Review
- Inhibition of mGluR5 alters BDNF/TrkB and GLT-1 expression in the prefrontal cortex and hippocampus and ameliorates PTSD-like behavior in rats.Psychopharmacology · 2023Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleGrowing evidence suggests that downregulated clearance of glutamate and signaling pathways involving brain-derived neurotrophic factor (BDNF) and its receptor TrkB play a role in morphological changes in the hippocampus of depressed patients. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is the most attractive antidepressant, although precise mechanisms are unknown.
objectiveIn this study, we examined whether hippocampal BDNF-TrkB signaling underlies the antidepressant effects of ketamine via upregulating glutamate transporter 1 (GLT-1) in rats, subjected to the chronic unpredictable stress (CUS) for 42 days. The rats received a single injection of ketamine (10 mg/kg, i.p.) and/or a TrkB inhibitor, K252a (1 μl, 2 mM, intracerebroventicular (i.c.v.)) on day 43. Behavioral tests and brain sample collection were evaluated 24 h later.
resultsThe CUS-exposed rats exhibited depression- and anxiety-like behaviors; decreased number of glial fibrillary acidic protein (GFAP)-positive (but not NeuN-positive) cells in the dentate gyrus (DG), CA1, and CA3 areas; increased number of cleaved caspase-3-positive astrocytes; reduced spine density; lower ratio of Bcl2 to Bax; and decreased levels of BDNF, phosphorylated cAMP response element binging protein (CREB), GLT-1, and postsynaptic density 95 (PSD95) proteins in the hippocampus. Ketamine alleviated the CUS-induced abnormalities. The effects of ketamine were antagonized by pretreatment with K252a.
conclusionsOur findings suggest that regulation of GLT-1 on astrocytes, responsible for 90 % of glutamate reuptake from the synapse, through BDNF-TrkB signaling is involved in mediation of the therapeutic effects of ketamine on behavioral abnormalities and morphological changes in the hippocampus of the CUS-exposed rats.
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