Perinatal Iron Deficiency Alters Apical Dendritic Growth in Hippocampal CA1 Pyramidal Neurons

Abstract

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.

Multiple mechanisms account for lower plasma iron in young copper deficient rats

“…Importantly, can iron repletion restore brain iron deficits in Cu− pups? If possible, this will aid in determining if the neurological abnormalities observed in both copper and iron deficiency, such as hippocampus immaturity, are independent or related (Hunt and Idso 1995;Jorgenson et al 2003). Milk copper (A) and iron (B) concentrations in Cu+ and Cu− rat dams milked at P19 (Experiment 1) and P20 (Experiment 2).…”

Iron Status and Neurobehavioral Development of Premature Infants

“…[9][10][11][12] More recent studies on iron status and the developing brain showed that perinatal iron deficiency affects dendritic growth and structure, neural metabolic activity, and synaptogenesis. [16][17][18]23,24 We hypothesized that these neural processes may also play an important role in determining the effect of low iron on reflexes reactivity.…”

“…In such models, decreases in brain iron content have been associated with electrophysiological alterations, impaired dopaminergic function, decreased cytochrome c oxidase activity, abnormal dendritic morphology, impaired myelin production, and long-term behavioral changes. [9][10][11][12][13][14][15][16][17][18] Tamura et al 19 has reported that cord serum ferritin levels in term human newborn infants correlated with ultimate cognitive function at 5 years of age. While such correlations do not confirm the causal relationship, given the multiple confounders in such study populations (as noted by Fleming,20 and Beard and Connor 21 ), these data suggest the importance of iron status for the developing brain.…”

The Role of Nutrition in Children's Neurocognitive Development, From Pregnancy Through Childhood

“…It is believed that iron is involved with different enzyme systems in the brain, including: the cytochrome c oxidase enzyme system in energy production, tyrosine hydroxylase for dopamine receptor synthesis, delta-9-desaturase for myelination, and fatty acid synthesis, and ribonucleotide reductase for brain growth regulation (Deungria, 2000;Lozoff and Georgieff, 2006;Georgieff, 2007;Rioux et al, 2011). In addition, iron appears to modify developmental processes in hippocampal neurons by altering dendritic growth (Jorgenson et al, 2003;Lozoff and Georgieff, 2006).…”