ArticlePsychopharmacology2022
Ketamine induces rapid antidepressant effects via the autophagy-NLRP3 inflammasome pathway.
Article in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Lipopolysaccharide-induced depression-like model in mice: meta-analysis and systematic evaluation.Frontiers in immunology · 2023Pooled it
- Investigation of Potential Therapeutic Effects of New Rapid-Acting Antidepressant Drugs (RAADs) Using Stress-Based Models of Depression.Biomolecules · 2026Review
- Sedation as an Immunomodulator of Inflammatory Responses in the Lung-Brain Axis of ARDS.International journal of molecular sciences · 2026Review
- Modulating NLRP3 Inflammasome Activity and Enhancing Cortical Synaptic Plasticity: Nanoparticulate Hydrogen's Role in Relief of Post-traumatic Anxiety-like Behaviors in Rats.Molecular neurobiology · 2025Article
- Chronic Stress Disrupts Immune and Endocrine Axis, Inducing Persistent Behavioral Impairments in Male Rats: In Silico and In Vivo Insights.Neurochemical research · 2025Article
- Autophagy Modulation by Antidepressants: Mechanisms and Implications.Neurochemical research · 2025Review
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- The Inflammasome-miR Axis in Alzheimer's Disease and Chronic Pain: Molecular Mechanisms and Therapeutic Opportunities.Aging and disease · 2025Review
- Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.Acta pharmacologica Sinica · 2025Article
- Time- and Region-specific Effect of Vortioxetine on Central LPS-induced Transcriptional Regulation of NLRP3 Inflammasome.Current neuropharmacology · 2025Article
- NLRP3 Inflammasome: A New Target for the Treatment of CVD and Depression Comorbidity.Mediators of inflammation · 2025Review
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook.Frontiers in psychiatry · 2025Review
- Effect of subanesthetic dose of esketamine on early postoperative depression in elderly patients with Sarcopenia.Journal of orthopaedic surgery and research · 2024Article
- New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD).Neurochemical research · 2024Review
- Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.Biomolecules & therapeutics · 2024Review
- Targeting Large-Conductance Calcium-Activated Potassium Channels to Ameliorate Lipopolysaccharide-Induced Depressive-Like Behavior in Mice.Neurochemical research · 2024Article
- Review
- Whole-Genome Metagenomic Analysis of the Oral Microbiota in Patients with Obstructive Sleep Apnea Comorbid with Major Depressive Disorder.Nature and science of sleep · 2024Article
- Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?Translational psychiatry · 2023Article
- Circulating Toll-Like Receptor 4, Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3, and Cytokines in Patients with Bipolar Depression: A Case-Control Study.Alpha psychiatry · 2023Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSub-anesthetic ketamine has rapid-onset effects for the treatment of major depressive disorder (MDD). However, the mechanism underlying ketamine's antidepressant properties remains unclear. Recent studies have reported an interrelationship between autophagy and the inflammasome, both of which are involved in the pathophysiology of MDD. In this study, we assess whether ketamine exerts its antidepressant effects via an association with the autophagy-NLRP3 inflammasome pathway.
methodsWe established a depressive-like rat model by treating Wistar Kyoto rats with chronic restraint stress (CRS) for 28 days. Microglial cells from newborn Sprague-Dawley rats were used for in vitro experiments.
resultsWe found sub-anesthetic ketamine treatment reversed depressive-like behavior in CRS rats. Ketamine triggered autophagy in the microglia of prefrontal cortex (PFC) and (hippocampus) HPC, with increased levels of LC3B, decreased levels of p62 protein, and elevated autophagosomes both in vivo and in vitro. Moreover, NLRP3 inflammasome activation was also inhibited by ketamine, with reduced expression of NLRP3-ASC-CASP1 assembly and decreased IL-1β levels in cerebrospinal fluid (CSF) as well as in the serum. Increased BDNF levels and synaptophysin levels were detected in the ketamine-treated group. The rapid anti-depressive effects, elevation of autophagy, reduction in NLRP3, and neuroplasticity-related factors induced by ketamine could be significantly blocked by the autophagy inhibitor Baf A1 (0.1 mg/kg).
conclusionsOur findings demonstrate that sub-anesthetic doses of ketamine exert their antidepressant-like effects by inhibiting inflammation and initiating neuroprotection via autophagy activation. These data might help expand future investigations on the antidepressant properties of ketamine.
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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.