Fetal and neonatal iron deficiency causes volume loss and alters the neurochemical profile of the adult rat hippocampus

Raghavendra Rao, Ivan Tkac, Adam T. Schmidt, Michael K. Georgieff

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Objective: Perinatal iron deficiency results in persistent hippocampus-based cognitive deficits in adulthood despite iron supplementation. The objective of the present study was to determine the long-term effects of perinatal iron deficiency and its treatment on hippocampal anatomy and neurochemistry in formerly iron-deficient young adult rats. Methods: Perinatal iron deficiency was induced using a low-iron diet during gestation and the first postnatal week in male rats. Hippocampal size was determined using volumetric magnetic resonance imaging at 8 weeks of age. Hippocampal neurochemical profile, consisting of 17 metabolites indexing neuronal and glial integrity, energy reserves, amino acids, and myelination, was quantified using high-field in vivo 1H NMR spectroscopy at 9.4 T (N = 11) and compared with iron-sufficient control group (N = 10). Results: The brain iron concentration was 56% lower than the control group at 7 days of age in the iron-deficient group, but had recovered completely at 8 weeks. The cross-sectional area of the hippocampus was decreased by 12% in the formerly iron-deficient group (P = 0.0002). The hippocampal neurochemical profile was altered: relative to the control group, creatine, lactate, N-acetylaspartylglutamate, and taurine concentrations were 6-29% lower, and glutamine concentration 18% higher in the formerly iron-deficient hippocampus (P < 0.05). Discussion: Perinatal iron deficiency was associated with reduced hippocampal size and altered neurochemistry in adulthood, despite correction of brain iron deficiency. The neurochemical changes suggest suppressed energy metabolism, neuronal activity, and plasticity in the formerly iron-deficient hippocampus. These anatomic and neurochemical changes are consistent with previous structural and behavioral studies demonstrating long-term hippocampal dysfunction following perinatal iron deficiency.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalNutritional Neuroscience
Issue number2
StatePublished - Mar 2011


  • H NMR spectroscopy
  • Hippocampus
  • Iron
  • Newborn
  • Perinatal iron deficiency


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