ArticleThe Journal of nutrition2024
Cellular Iron Deficiency Disrupts Thyroid Hormone Regulated Gene Expression in Developing Hippocampal Neurons.
Article in The Journal of nutrition, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 3 citations in OpenAlex.
- Iron Deficiency Impairs Mitochondrial Energetics and Early Axonal Growth and Branching in Developing Hippocampal Neurons.The Journal of nutrition · 2026Article
- Novel SLC16A2 mutations impair thyroid hormone transport and drive neurodevelopmental deficits in Chinese patients with allan-herndon-dudley syndrome.Scientific reports · 2026Article
- Emerging Roles, Mechanisms, and Therapeutic Potential of Thyroid Hormones in Neurodegenerative Diseases: A Review.Brain sciences · 2026Review
- Iron deficiency aggravates hepatic inflammation in suckling piglets via endoplasmic reticulum stress-driven NF-κB pathway activation.Journal of animal science and biotechnology · 2026Article
- Neonatal phlebotomy-induced anemia compromises mitochondrial bioenergetics in the developing hippocampus.bioRxiv : the preprint server for biology · 2025Article
- Iron Deficiency Impairs Mitochondrial Energetics and Early Axonal Growth and Branching in Developing Hippocampal Neurons.bioRxiv : the preprint server for biology · 2025Article
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7 authors at 1 institution in 1 country.
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Abstract
backgroundDeveloping neurons have high thyroid hormone and iron requirements to support their metabolically demanding growth. Early-life iron and thyroid-hormone deficiencies are prevalent and often coexist, and each independently increases risk of permanently impaired neurobehavioral function in children. Early-life dietary iron deficiency reduces thyroid-hormone concentrations and impairs thyroid hormone-responsive gene expression in the neonatal rat brain, but it is unclear whether the effect is cell-intrinsic.
objectivesThis study determined whether neuronal-specific iron deficiency alters thyroid hormone-regulated gene expression in developing neurons.
methodsIron deficiency was induced in primary mouse embryonic hippocampal neuron cultures with the iron chelator deferoxamine (DFO) beginning at 3 d in vitro (DIV). At 11DIV and 18DIV, thyroid hormone-regulated gene messenger ribonucleic acid (mRNA)concentrations indexing thyroid hormone homeostasis (Hairless, mu-crystallin, Type II deiodinase, solute carrier family member 1c1, and solute carrier family member 16a2) and neurodevelopment (neurogranin, Parvalbumin, and Krüppel-like factor 9) were quantified. To assess the effect of iron repletion, DFO was removed at 14DIV from a subset of DFO-treated cultures, and gene expression and adenosine 5'-triphosphate (ATP) concentrations were quantified at 21DIV.
resultsAt 11DIV and 18DIV, neuronal iron deficiency decreased neurogranin, Parvalbumin, and mu-crystallin, and by 18DIV, solute carrier family member 16a2, solute carrier family member 1c1, Type II deiodinase, and Hairless were increased, suggesting cellular sensing of a functionally abnormal thyroid hormone state. Dimensionality reduction with Principal component analysis reveals that thyroid hormone homeostatic genes strongly correlate with and predict iron status. Iron repletion from 14-21DIV did not restore ATP concentration, and Principal component analysis suggests that, after iron repletion, cultures maintain a gene expression signature indicative of previous iron deficiency.
conclusionsThese novel findings suggest there is an intracellular mechanism coordinating cellular iron/thyroid hormone activities. We speculate this is a part of the homeostatic response to acutely match neuronal energy production and growth signaling. However, the adaptation to iron deficiency may cause permanent deficits in thyroid hormone-dependent neurodevelopmental processes even after recovery from iron deficiency.
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