The Role of Iron in Learning and Memory

Abstract

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.

Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis

“…Thus, although some of the epigenetic effects of iron deprivation appear to be more transient, others are maintained across multiple cell cycles. This suggests that iron deprivation may have lasting effects on gene regulatory programs and offers potential mechanistic insights into observations that iron deprivation leads to a lasting developmental delay, which has been demonstrated to persist beyond iron readministration (42,43).…”

Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

“…Of the original 102 infants (946 6 196 g, 27.7 6 1.8 weeks' gestation), 80 (29 Epo,27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age.…”

“…Adequate iron is vital to brain development, and previous investigators have postulated that infants receiving Epo would be at risk for neurodevelopmental impairment owing to available iron being shunted to red cells at the expense of the brain. 27 Despite monitoring ferritin during the study and adjusting dosing 27 (100) 27 (93) 23 (96) accordingly, infants in the ESA groups had lower ferritin at 14 and 42 days. 12 The improved outcomes in ESA-treated infants, despite reduced ferritin values, suggest that ESA treatment may be beneficial even in the setting of reduced iron availability, and may be even more beneficial when adequate iron stores are achieved.…”

Deficiencia de micronutrientes y enfermedad celíaca en pediatría

“…11 En la EC, se ha encontrado el síndrome anémico como la única manifestación clínica o como la manifestación clínica más frecuente de EC extraintestinal. La anemia nutricional es más común en celíacos; se manifiesta como anemia microcítica, hipocrómica, con concentraciones bajas de Fe sérico, elevación de la capacidad total de ligar Fe y bajas concentraciones de ferritina sérica.…”