The Role of Iron in Learning and Memory
Open accessAbstract
Iron deficiency (ID) is the most common nutrient deficiency, affecting 2 billion people and 30% of pregnant women and their offspring. Early life ID affects at least 3 major neurobehavioral domains, including speed of processing, affect, and learning and memory, the latter being particularly prominent. The learning and memory deficits occur while the infants are iron deficient and persist despite iron repletion. The neural mechanisms underlying the short- and long-term deficits are being elucidated. Early ID alters the transcriptome, metabolome, structure, intracellular signaling pathways, and electrophysiology of the developing hippocampus, the brain region responsible for recognition learning and memory. Until recently, it was unclear whether these effects are directly due to a lack of iron interacting with important transcriptional, translational, or post-translational processes or to indirect effects such as hypoxia due to anemia or stress. Nonanemic genetic mouse models generated by conditionally altering expression of iron transport proteins specifically in hippocampal neurons in late gestation have led to a greater understanding of iron's role in learning and memory. The learning deficits in adulthood likely result from interactions between direct and indirect effects that contribute to abnormal hippocampal structure and plasticity.
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Iron is essential for neuronal development, myelination of nerve fibers, mitochondrial function, and hippocampus development.
“Iron is very important for neuronal development and is essential for the myelination of nerve fibers, mitochondrial function, and hippocampus development.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [97]
Iron deficiency has a negative effect on learning and memory, neurotransmitter synthesis such as dopamine, serotonin, norepinephrine, GABA, and acts as an enzyme co-factor.
“Its deficiency has a negative effect on learning and memory, neurotransmitter synthesis such as dopamine, serotonin, norepinephrine, Gamma-aminobutyric acid (GABA), and acts as an enzyme co-factor [96,97].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [97]
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Self-citationNatural selection on HFE in Asian populations contributes to enhanced non-heme iron absorption
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Does any drug to treat cancer target mTOR and iron hemostasis in neurodegenerative disorders?
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Iron status and anaemia in Sri Lankan secondary school children: A cross-sectional survey
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- Authors
- Fretham, S. J. B., Carlson, E. S., & Georgieff, M. K.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Georgieff, Michael K.
- Venue
- Advances in Nutrition
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 2
- Issue
- 2
- Pages
- 112-121
- ISSN
- 2156-5376 (ISSN-L)
- 2161-8313
- PMC
- PMC3065765
- OpenAlex
- W2097509137
- Cited by
- 235
- References
- 115
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 18 · 2023: 15 · 2022: 16 · 2021: 21 · 2020: 10 · 2019: 14 · 2018: 20 · 2017: 21 · 2016: 22 · 2015: 24 · 2014: 14 · 2013: 13 · 2012: 5
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Advances in Nutrition (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HD039386)
- National Institute of Neurological Disorders and Stroke (F31NS063667, F31NS047876)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD29421, R21HD054490, R01HD029421, P01HD039386)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- iron deficiency, learning and memory, hippocampus, neurobehavioral deficits, iron repletion, iron transport proteins, mouse model, hypoxia, anemia, hippocampal plasticity, intracellular signaling
- MeSH terms
- Iron Deficiencies, Adolescent, Adult, Animals, Child, Child, Preschool, Female, Hippocampus, Humans, Infant, Infant, Newborn, Learning, Memory, Neurons, Pregnancy, Trace Elements, Gene Expression, Brain-Derived Neurotrophic Factor, Iron, Dietary, Mice, Rats, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases
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