ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Brain iron loading impairs DNA methylation and alters GABAergic function in mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Iron dyshomeostasis and its neurobiological mechanisms in psychiatric disorders.Molecular psychiatry · 2026Review
- Associative Analysis of lncRNA/circRNA-miRNA-mRNA Expression Profiles in Iron-Overloaded HT-1080 Fibrosarcoma Cells.International journal of molecular sciences · 2026Article
- Homeostatic control of energy metabolism by monocyte-derived macrophages.The EMBO journal · 2026Article
- Essential element and toxic metal dyshomeostasis in childhood autism spectrum disorder: a comprehensive narrative review of correlations, tissue-specific distribution, and multifactorial regulation.Frontiers in behavioral neuroscience · 2026Review
- Dietary iron attenuates epigenetic aging through DNA methylation remodeling and extends survival in older adults.Clinical epigenetics · 2025Article
- Targeting mitochondria with natural polyphenols for treating Neurodegenerative Diseases: a comprehensive scoping review from oxidative stress perspective.Journal of translational medicine · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Intranasal delivery of iron chelators and management of central nervous system disease.Frontiers in pharmacology · 2025Review
- Ethanolic and aqueous extracts ofIBRO neuroscience reports · 2024Article
- Epigenetic regulation of targeted ferroptosis: A new strategy for drug development.Journal of pharmaceutical analysis · 2024Review
- Evaluating the Protective Effects of Melatonin Against Chronic Iron Administration in Male Wistar Rats: a Comparative Analysis of Affective, Cognitive, and Oxidative Stress with EDTA Chelator.Biological trace element research · 2024Article
- HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.International journal of molecular sciences · 2024Review
- Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study.Clinical epigenetics · 2023Article
- Ferroptosis in colorectal cancer: a future target?British journal of cancer · 2023Review
- The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review.eNeuro · 2023Review
- Psychostimulants influence oxidative stress and redox signatures: the role of DNA methylation.Redox report : communications in free radical research · 2022Review
- Regulators of epigenetic change in ferroptosis‑associated cancer (Review).Oncology reports · 2022Review
- Dysregulation of SOX17/NRF2 axis confers chemoradiotherapy resistance and emerges as a novel therapeutic target in esophageal squamous cell carcinoma.Journal of biomedical science · 2022Article
- Elevated transferrin saturation in individuals with alcohol use disorder: Association with HFE polymorphism and alcohol withdrawal severity.Addiction biology · 2022Article
- Iron Promotes Cardiac Doxorubicin Retention and Toxicity Through Downregulation of the Mitochondrial Exporter ABCB8.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Iron deficiency is closely associated with altered GABA metabolism and affective behavior. While mutation in the hemochromatosis ( HFE) gene disrupts iron homeostasis and promotes oxidative stress that increases the risk of neurodegeneration, it is largely unknown whether HFE mutation modifies GABAergic homeostasis and emotional behavior. The goal of our study was to investigate the impact of HFE on GABAergic neurochemistry and redox-epigenetic regulation in the brain using H67D HFE-mutant mice that recapitulates the H63D-HFE mutation in humans. H67D mice displayed elevated redox-active iron levels in the brain by 32% compared to age-matched wild-type mice. Moreover, the H67D brain had increased isoprostane and decreased glutathione, indicating elevated oxidative stress. Additionally, the H67D brain had decreased global methylation and attenuated DNA methyltransferase (DNMT) activity. Direct addition of iron to purified DNMT in vitro decreased enzyme activity in a concentration-dependent manner. Last, H67D mice exhibited decreased anxiety-like behavior, which was associated with increased expression of the GABA
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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.