ArticleTranslational psychiatry2020
Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β1.
Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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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.
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Who cites it
62 citing papers in PubMed, 117 citations in OpenAlex.
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers.Molecular psychiatry · 2026Review
- Research Progress on the Biological Function and Homeostatic Disruption of Microglia in the Pathogenesis of Major Depressive Disorder.Neuroscience bulletin · 2026Review
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Arketamine: a scoping review of its use in humans.European archives of psychiatry and clinical neuroscience · 2025Article
- Are "mystical experiences" essential for antidepressant actions of ketamine and the classic psychedelics?European archives of psychiatry and clinical neuroscience · 2025Review
- Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.European archives of psychiatry and clinical neuroscience · 2025Review
- Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways.Science advances · 2025Article
- Microglia Sing the Prelude of Neuroinflammation-Associated Depression.Molecular neurobiology · 2025Review
- The impact and mechanisms of YL-IPA08, a potent ligand for the translocator protein (18 kDa) on protection against LPS-induced depression and cognitive dysfunction in rodents.Metabolic brain disease · 2025Article
- CELF1 Promotes Post-myocardial Infarction Cardiac Remodeling Via Suppression of FMO2.Cardiovascular toxicology · 2025Article
- Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations.Clinical pharmacology and therapeutics · 2025Review
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook.Frontiers in psychiatry · 2025Review
- Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.IBRO neuroscience reports · 2024Article
- TGF-β Signaling in Microglia: A Key Regulator of Development, Homeostasis and Reactivity.Biomedicines · 2024Review
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions.Journal of anesthesia and translational medicine · 2024Review
- Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?Molecular psychiatry · 2024Review
- Esketamine Prevents Postoperative Emotional and Cognitive Dysfunction by Suppressing Microglial M1 Polarization and Regulating the BDNF-TrkB Pathway in Ageing Rats with Preoperative Sleep Disturbance.Molecular neurobiology · 2024Article
- BioM2: biologically informed multi-stage machine learning for phenotype prediction using omics data.Briefings in bioinformatics · 2024Article
- Myelin-associated oligodendrocytic basic protein-dependent myelin repair confers the long-lasting antidepressant effect of ketamine.Molecular psychiatry · 2024Article
- The role of NMDARs in the anesthetic and antidepressant effects of ketamine.CNS neuroscience & therapeutics · 2024Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
In rodent models of depression, (R)-ketamine has greater potency and longer-lasting antidepressant effects than (S)-ketamine; however, the precise molecular mechanisms underlying the antidepressant actions of (R)-ketamine remain unknown. Using RNA-sequencing analysis, we identified novel molecular targets that contribute to the different antidepressant effects of the two enantiomers. Either (R)-ketamine (10 mg/kg) or (S)-ketamine (10 mg/kg) was administered to susceptible mice after chronic social defeat stress (CSDS). RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent GSEA (gene set enrichment analysis) revealed that transforming growth factor (TGF)-β signaling might contribute to the different antidepressant effects of the two enantiomers. (R)-ketamine, but not (S)-ketamine, ameliorated the reduced expressions of Tgfb1 and its receptors (Tgfbr1 and Tgfbr2) in the PFC and hippocampus of CSDS susceptible mice. Either pharmacological inhibitors (i.e., RepSox and SB431542) or neutralizing antibody of TGF-β1 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Moreover, depletion of microglia by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Similar to (R)-ketamine, the recombinant TGF-β1 elicited rapid and long-lasting antidepressant effects in animal models of depression. Our data implicate a novel microglial TGF-β1-dependent mechanism underlying the antidepressant effects of (R)-ketamine in rodents with depression-like phenotype. Moreover, TGF-β1 and its receptor agonists would likely constitute a novel rapid-acting and sustained antidepressant in humans.
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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.