ArticleMolecular psychiatry2023
Targeting PDK2 rescues stress-induced impaired brain energy metabolism.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Phenotype-Specific Transcriptomic Responses to Glucocorticoid Signaling in the Prefrontal Cortex and Dorsal Raphe Nucleus Following Chronic Social Stress.International journal of molecular sciences · 2026Article
- Glucocorticoids combined with anticoagulation modulate the central NLRP3/NETosis inflammatory process in patients with severe cerebral venous thrombosis: a human mechanistic exploratory study.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Meconium metabolomic profiling dysregulation and neonatal brain injury in selective fetal growth restriction.BMC pregnancy and childbirth · 2026Article
- Extracellular vesicle therapeutics in Alzheimer's disease: mechanisms, progress, and prospects.Extracellular vesicles and circulating nucleic acids · 2026Review
- Metabolomic landscape of fetal organ development during late gestation in mice.Communications biology · 2025Article
- Exploring the shared genetic architecture between testosterone traits and major depressive disorder.BMC psychiatry · 2025Article
- Multi-dimensional data-driven computational drug repurposing strategy for screening novel neuroprotective agents in ischemic stroke.Theranostics · 2025Article
- Multi-omics derivation of a core gene signature for predicting therapeutic response and characterizing immune dysregulation in inflammatory bowel disease.Frontiers in immunology · 2025Article
- Causal Links Between Cerebrospinal Fluid Metabolites and Postpartum Depression: A Bidirectional Mendelian Randomization Study.International journal of women's health · 2025Article
- The Mitochondrial Blueprint: Unlocking Secondary Metabolite Production.Metabolites · 2024Review
- A novel PDHK inhibitor restored cognitive dysfunction and limited neurodegeneration without affecting amyloid pathology in 5xFAD mouse, a model of Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Simulated weightlessness procedure, head-down bed rest has reversible effects on the metabolism of rhesus macaque.Molecular brain · 2024Article
- Transcutaneous auricular vagus nerve stimulation ameliorates adolescent depressive- and anxiety-like behaviors via hippocampus glycolysis and inflammation response.CNS neuroscience & therapeutics · 2024Article
- Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study.Frontiers in psychiatry · 2024Article
- Resilience and Vulnerability to Stress-Induced Anhedonia: Unveiling Brain Gene Expression and Mitochondrial Dynamics in a Mouse Chronic Stress Depression Model.Biomolecules · 2023Article
- Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Depression is a mental illness frequently accompanied by disordered energy metabolism. A dysregulated hypothalamus pituitary adrenal axis response with aberrant glucocorticoids (GCs) release is often observed in patients with depression. However, the associated etiology between GCs and brain energy metabolism remains poorly understood. Here, using metabolomic analysis, we showed that the tricarboxylic acid (TCA) cycle was inhibited in chronic social defeat stress (CSDS)-exposed mice and patients with first-episode depression. Decreased mitochondrial oxidative phosphorylation was concomitant with the impairment of the TCA cycle. In parallel, the activity of pyruvate dehydrogenase (PDH), the gatekeeper of mitochondrial TCA flux, was suppressed, which is associated with the CSDS-induced neuronal pyruvate dehydrogenase kinase 2 (PDK2) expression and consequently enhanced PDH phosphorylation. Considering the well-acknowledged role of GCs in energy metabolism, we further demonstrated that glucocorticoid receptors (GR) stimulated PDK2 expression by directly binding to its promoter region. Meanwhile, silencing PDK2 abrogated glucocorticoid-induced PDH inhibition, restored the neuronal oxidative phosphorylation, and improved the flux of isotope-labeled carbon (U-
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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 Socratic graph.