Perinatal iron deficiency alters apical dendritic growth in hippocampal CA1 pyramidal neurons

Dev Neurosci. 2003 Nov-Dec;25(6):412-20. doi: 10.1159/000075667.


Iron deficiency early in life is associated with cognitive disturbances that persist beyond the period of iron deficiency. Within cognitive processing circuitry, the hippocampus is particularly susceptible to insults during the perinatal period. During the hippocampal growth spurt, which is predominantly postnatal in rodents, iron transport proteins and their messenger RNA stabilizing proteins are upregulated, suggesting an increased demand for iron import during this developmental period. Rat pups deprived of iron during the perinatal period show a 30-40% decrease in hippocampal metabolic activity during postnatal hippocampal development. We hypothesized that this reduced hippocampal neuronal metabolism impedes developmental processes such as neurite outgrowth. The goals of the current study were to investigate the effects of perinatal iron deficiency on apical dendritic segment growth in the postnatal day (P) 15 hippocampus and to determine if structural abnormalities persist into adulthood (P65) following iron treatment. Qualitative and quantitative immunohistochemical analyses of dendritic structure and growth using microtubule-associated protein-2 as an index showed that iron-deficient P15 pups have truncated apical dendritic morphology in CA1 and a persistence of an immature apical dendritic pattern at P65. These results demonstrate that perinatal iron deficiency disrupts developmental processes in the hippocampal subarea CA1 and that these changes persist despite iron repletion. These structural abnormalities may contribute to the learning and memory deficits that occur during and following early iron deficiency.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Dendrites / metabolism*
  • Dendrites / pathology
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Female
  • Fluorescent Antibody Technique
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Iron / pharmacology
  • Iron Deficiencies*
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Organ Size / drug effects
  • Organ Size / physiology
  • Prenatal Nutritional Physiological Phenomena / physiology
  • Pyramidal Cells / metabolism*
  • Pyramidal Cells / pathology
  • Rats
  • Rats, Sprague-Dawley


  • Microtubule-Associated Proteins
  • Iron