ArticleMolecular psychiatry2022
Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 97 papers, 3 of them syntheses that pooled it.
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Who cites it
97 citing papers in PubMed, 3 syntheses or guidelines pooled it, 199 citations in OpenAlex.
- Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Pooled it
- CREB: A Promising Therapeutic Target for Treating Psychiatric Disorders.Current neuropharmacology · 2024Pooled it
- Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies.Molecular psychiatry · 2023Pooled it
- Inhibition of Abnormal Elevated α-Synuclein Ameliorates Dopaminergic Neuron Degeneration in Parkinson's Disease Mouse Model.Aging cell · 2026Article
- Association of the red blood cell distribution width-to-albumin ratio with incident depression and depressive symptom trajectories in older adults.European archives of psychiatry and clinical neuroscience · 2026Article
- Semaglutide exerts neuroprotective effects by blocking the interleukin-17/NOD-like receptor family pyrin domain containing 3-mediated neuroinflammation pathway after traumatic brain injury.Neural regeneration research · 2026Article
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers.Molecular psychiatry · 2026Review
- Antidepressant-like effects of ketamine involve CXTranslational psychiatry · 2026Article
- Microglia-Dependent BDNF Signaling in the Dentate Gyrus Underlies the Antidepressant Effects of Gardiquimod, a Toll-Like Receptor 7 Agonist, in Chronically Stressed Mice.Neurochemical research · 2026Article
- DNA Methylation Regulates CDK5R1 and NRBP1 to Exert Effects on Alcohol Dependence: Insights From Mendelian Randomization.Addiction biology · 2026Article
- Research Progress on the Biological Function and Homeostatic Disruption of Microglia in the Pathogenesis of Major Depressive Disorder.Neuroscience bulletin · 2026Review
- Cerebrum functional network alterations following posterior fossa surgery in Children.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Defining functional states and roles of microglia in neuropsychiatric disorders.Frontiers in cellular neuroscience · 2026Review
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Clinical research progress of esketamine in perioperative neuroprotection: from mechanisms to therapeutic neuroprotection.Frontiers in pharmacology · 2026Review
- Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation.International journal of molecular sciences · 2025Review
- Intestinal γδ T17-IL-17A signaling disrupts hippocampal mitophagy in stress-induced depression and is restored by arketamine.Journal of neuroinflammation · 2025Article
- Integrative multi-omics analysis of druggable genes for therapeutic target identification in polycystic ovary syndrome.Journal of ovarian research · 2025Article
- Oligogenic risk score for Gilles de la Tourette syndrome reveals a genetic continuum of tic disorders.Journal of applied genetics · 2025Article
- Effects of esketamine on electrophysiology and metabolic reprogramming in brain organoids: insights into antidepressant mechanisms.Molecular psychiatry · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
(R,S)-ketamine elicits rapid-acting and sustained antidepressant actions in treatment-resistant patients with depression. (R)-ketamine produces longer-lasting antidepressant effects than (S)-ketamine in rodents; however, the precise molecular mechanisms underlying antidepressant actions of (R)-ketamine remain unknown. Using isobaric Tag for Relative and Absolute Quantification, we identified nuclear receptor-binding protein 1 (NRBP1) that could contribute to different antidepressant-like effects of the two enantiomers in chronic social defeat stress (CSDS) model. NRBP1 was localized in the microglia and neuron, not astrocyte, of mouse medial prefrontal cortex (mPFC). (R)-ketamine increased the expression of NRBP1, brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element binding protein (p-CREB)/CREB ratio in primary microglia cultures thorough the extracellular signal-regulated kinase (ERK) activation. Furthermore, (R)-ketamine could activate BDNF transcription through activation of CREB as well as MeCP2 (methyl-CpG binding protein 2) suppression in microglia. Single intracerebroventricular (i.c.v.) injection of CREB-DNA/RNA heteroduplex oligonucleotides (CREB-HDO) or BDNF exon IV-HDO blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Moreover, microglial depletion by colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. In addition, inhibition of microglia by single i.c.v. injection of mannosylated clodronate liposomes (MCLs) significantly blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Finally, single i.c.v. injection of CREB-HDO, BDNF exon IV-HDO or MCLs blocked the beneficial effects of (R)-ketamine on the reduced dendritic spine density in the mPFC of CSDS susceptible mice. These data suggest a novel ERK-NRBP1-CREB-BDNF pathways in microglia underlying antidepressant-like effects of (R)-ketamine.
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