ArticleTranslational psychiatry2022
Nuclear factor of activated T cells 4 in the prefrontal cortex is required for prophylactic actions of (R)-ketamine.
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.Psychopharmacology · 2025Pooled it
- Esketamine as an Adjuvant to Ropivacaine in Genicular Nerve and IPACK Blocks for Total Knee Arthroplasty: A Double-Blind Randomized Trial.Drug design, development and therapy · 2025Trial
- Intermittent fasting protects against stress-induced depression and demyelination via the gut microbiota-brain axis.Translational psychiatry · 2026Article
- Non-randomized rapamycin augmentation of chronic self-administered ketamine provides subjective improvement in diverse phenotypes.Frontiers in psychiatry · 2026Article
- Downregulation of p120 catenin in the mouse hippocampus contributes to the development of depression-like phenotypes.Behavioral and brain functions : BBF · 2025Article
- Central-peripheral neuroimmune dynamics in psychological stress and depression: insights from current research.Molecular psychiatry · 2025Review
- S-ketamine relieves neuropathic pain by inhibiting microglia phagocytosis of the perineuronal nets.Scientific reports · 2025Article
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms.Biomedicines · 2024Review
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions.Journal of anesthesia and translational medicine · 2024Review
- Cerebrospinal fluid metabolomes of treatment-resistant depression subtypes and ketamine response: a pilot study.Discover mental health · 2024Article
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.Frontiers in pharmacology · 2024Review
- Rapamycin Augmentation of Chronic Ketamine as a Novel Treatment for Complex Regional Pain Syndrome.Cureus · 2023Article
- A role of splenic heme biosynthesis pathway in the persistent prophylactic actions of arketamine in lipopolysaccharide-treated mice.Translational psychiatry · 2023Article
- The antidepressant actions of ketamine and its enantiomers.Pharmacology & therapeutics · 2023Review
- Inflammation, stress and depression: An exploration of ketamine's therapeutic profile.Drug discovery today · 2023Review
- Impact of broad-spectrum antibiotics on the gut-microbiota-spleen-brain axis.Brain, behavior, & immunity - health · 2023Article
- Gut-microbiota-brain axis in the vulnerability to psychosis in adulthood after repeated cannabis exposure during adolescence.European archives of psychiatry and clinical neuroscience · 2022Article
- A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice.Translational psychiatry · 2022Article
- Effects of splenectomy on skin inflammation and psoriasis-like phenotype of imiquimod-treated mice.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
(R, S)-ketamine has prophylactic antidepressant-like effects in rodents; however, the precise molecular mechanisms underlying its action remain unknown. Using RNA-sequencing analysis, we searched novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R, S)-ketamine. Pretreatment with (R)-ketamine (10 mg/kg, 6 days before) significantly ameliorated body weight loss, splenomegaly, and increased immobility time of forced swimming test in lipopolysaccharide (LPS: 1.0 mg/kg)-treated mice. RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent IPA (Ingenuity Pathway Analysis) revealed that the nuclear factor of activated T cells 4 (NFATc4) signaling might contribute to sustained prophylactic effects of (R)-ketamine. Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated the increased gene expression of NFATc4 signaling (Nfatc4, Cd4, Cd79b, H2-ab1, H2-aa) in the PFC of LPS-treated mice. Furthermore, pretreatment with NFAT inhibitors (i.e., NFAT inhibitor and cyclosporin A) showed prophylactic effects in the LPS-treated mice. Similar to (R)-ketamine, gene knockdown of Nfatc4 gene by bilateral injection of adeno-associated virus (AAV) into the mPFC could elicit prophylactic effects in the LPS-treated mice. In conclusion, our data implicate a novel NFATc4 signaling pathway in the PFC underlying the prophylactic effects of (R)-ketamine for inflammation-related depression.
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