ArticleJournal of neuroinflammation2023
Nrf2 regulates iron-dependent hippocampal synapses and functional connectivity damage in depression.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Association between iron deposition and emotional disorder in Parkinson's patients: a systematic review and meta-analysis.BMC neurology · 2026Pooled it
- Ferroptosis in depression: mechanisms, association, and therapeutic strategies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Hippocampal Volume Mediates the Association Between Serum Ferritin and Cognition in Non-Dialysis End-Stage Renal Disease Patients.Brain and behavior · 2026Article
- Iron dyshomeostasis and its neurobiological mechanisms in psychiatric disorders.Molecular psychiatry · 2026Review
- Dysregulation of local inhibitory inputs onto laterodorsal tegmental nucleus cholinergic neurons drives depression-like behaviors in mice.Molecular psychiatry · 2026Article
- The NO-cGMP signaling pathway and depression: mechanisms and therapeutic prospects.Molecular biology reports · 2026Review
- Carboxypeptidase E Alleviates Depressive-Like Behaviors in Mice by Regulating BDNF/Nrf2 Axis-Mediated Ferroptosis.Neurochemical research · 2026Article
- Exposure to multiple metals and adolescent major depressive disorder: a case-control study in China.BMC psychiatry · 2026Article
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- Methamphetamine hijacks chaperone-mediated autophagy to degrade GPX4, driving ferroptosis-precipitated cognitive decline and addictive pathogenesis.Acta neuropathologica communications · 2026Article
- Nutrients and Functional Components of Medicine and Food Homology Substances on Antidepressant Effects: A Mechanism-Oriented Review.Molecules (Basel, Switzerland) · 2026Review
- Ferroptosis in Neuropsychiatric and Neurodegenerative Disorders: Shared Mechanisms and Disease-Specific Signatures.Pharmaceuticals (Basel, Switzerland) · 2026Review
- DIRAS2 modulates MAPK pathway-mediated ferroptosis to regulate excitation/inhibition balance and seizure susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Relationship Between Trace Elements and Depression.Nutrients · 2026Review
- Astrocytic PCBP1 Suppresses Ferroptosis to Restore Glutamatergic Homeostasis and Mitigate Stress-Induced Depression in Male Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Polystyrene nanoplastics-induced lung epithelial cells ferroptosis promotes pulmonary fibrosis via YY1/FTL axis.Materials today. Bio · 2026Article
- Iron dyshomeostasis in neuropsychiatric disorders.Frontiers in psychiatry · 2026Review
- Interplay between the gut microbiota and MAPK/NF-κ B/Nrf2 signaling in depression: pharmacological insights from traditional Chinese medicine.Frontiers in pharmacology · 2026Review
- Role of TRPC1 in the pathogenesis of depression induced by traumatic brain injury.Frontiers in neuroscience · 2026Article
- Electroacupuncture alleviates comorbid obesity and depression via the gut-brain axis: orchestrating SCFA-producing bacteria and hippocampal synaptic plasticity.Frontiers in microbiology · 2026Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
Abstract
Neuronal iron overload contributes to synaptic damage and neuropsychiatric disorders. However, the molecular mechanisms underlying iron deposition in depression remain largely unexplored. Our study aims to investigate how nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) ameliorates hippocampal synaptic dysfunction and reduces brain functional connectivity (FC) associated with excessive iron in depression. We treated mice with chronic unpredictable mild stress (CUMS) with the iron chelator deferoxamine mesylate (DFOM) and a high-iron diet (2.5% carbonyl iron) to examine the role of iron overload in synaptic plasticity. The involvement of Nrf2 in iron metabolism and brain function was assessed using molecular biological techniques and in vivo resting-state functional magnetic resonance imaging (rs-fMRI) through genetic deletion or pharmacologic activation of Nrf2. The results demonstrated a significant correlation between elevated serum iron levels and impaired hippocampal functional connectivity (FC), which contributed to the development of depression-induced CUMS. Iron overload plays a crucial role in CUMS-induced depression and synaptic dysfunction, as evidenced by the therapeutic effects of a high-iron diet and DFOM. The observed iron overload in this study was associated with decreased Nrf2 levels and increased expression of transferrin receptors (TfR). Notably, inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Nrf2
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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.