ArticleRedox biology2016
Uncoupling protein 2 modulation of the NLRP3 inflammasome in astrocytes and its implications in depression.
Article in Redox biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Natural antidepressants in neuroimmunomodulation: molecular mechanisms, action targets, and therapeutic potential.Frontiers in immunology · 2025Pooled it
- Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.Biological psychiatry · 2021Pooled it
- Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration.Neural regeneration research · 2026Article
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- From mitochondrial oxidative stress to neuroinflammation: integrated proteomic and transcriptomic profiling reveals the role of the ROS/TXNIP/NLRP3 signaling pathway in anxious depression.Frontiers in immunology · 2026Article
- Deciphering the mechanistic involvement of PANoptosis in FC-MDD comorbidity through the gut-brain axis.Frontiers in immunology · 2026Review
- Research Progress of Functionalized Drug Delivery Nanosystems in Regulating Depression.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Superoxide Anion-Dependent Mitochondrial Fission Contributes to Hippocampal Synaptic Dysfunction in Stress-Susceptible Mice.JACS Au · 2025Article
- Carotid Plaque-Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability.MedComm · 2025Article
- The Role of Mitochondrial Energy Metabolism in the Mechanism of Exercise Improving Depression.Current issues in molecular biology · 2025Review
- Neuroinflammation-A Crucial Factor in the Pathophysiology of Depression-A Comprehensive Review.Biomolecules · 2025Review
- Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases.Cell death & disease · 2025Article
- Bioenergetic-related gene expression in the hippocampus predicts internalizing vs. externalizing behavior in an animal model of temperament.Frontiers in molecular neuroscience · 2025Article
- Single-cell transcriptome-wide Mendelian randomization identifies mitochondrial targets in immune cells for Major Depressive Disorder.Frontiers in immunology · 2025Article
- Research Trends and Evolution of Astrocytes in Depression and Antidepressant Treatment: A Bibliometric Analysis.Current neuropharmacology · 2025Article
- Altered leptin signaling and attenuated cardiac vagal activity in rats with type 2 diabetes.Frontiers in physiology · 2025Article
- Bone marrow mesenchymal stem cells-derived exosomes promote spinal cord injury repair through the miR-497-5p/TXNIP/NLRP3 axis.Journal of molecular histology · 2024Article
- The Neglected Sibling: NLRP2 Inflammasome in the Nervous System.Aging and disease · 2024Review
- The role of exercise-related FNDC5/irisin in depression.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial uncoupling protein 2 (UCP2) has been well characterized to control the production of reactive oxygen species (ROS) and astrocytes are the major cells responsible for the ROS production and the inflammatory responses in the brain. However, the function of UCP2 in astrocytes and the contribution of astrocytic UCP2 to depression remain undefined. Herein, we demonstrated that UCP2 knockout (KO) mice displayed aggravated depressive-like behaviors, impaired neurogenesis, and enhanced loss of astrocytes in the chronic mild stress (CMS)-induced anhedonia model of depression. We further found that UCP2 ablation significantly enhanced the activation of the nod-like receptor protein 3 (NLRP3) inflammasome in the hippocampus and in astrocytes. Furthermore, UCP2 deficiency promoted the injury of mitochondria, the generation of ROS and the physical association between thioredoxin-interacting protein (TXNIP) and NLRP3 in astrocytes. Moreover, transiently expressing exogenous UCP2 partially rescued the deleterious effects of UCP2 ablation on the astrocytes. These data indicate that UCP2 negatively regulates the activation of NLRP3 inflammasome and inhibited the ROS-TXNIP-NLRP3 pathway in astrocytes. Collectively, our findings reveal that UCP2 regulates inflammation responses in astrocytes and plays an important role in the pathogenesis of depression and that UCP2 may be a promising therapeutic target for depression.
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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.