Early iron deficiency anemia alters structure in pyramidal neuron apical dendrites and cytoskeletal modifiers associated with dendrite development in the hippocampus.

Abstract

Using a dietary model in Sprague Dawley rats of gestational/neonatal iron deficiency, our lab has demonstrated structural, biochemical, electrophysiological and behavioral changes in the developing hippocampus. The high energy demands of the developing hippocampus make it particularly vulnerable to iron deficits. At gestational day two, the pregnant dams were given iron deficient (ID) chow to induce approximately 50 % brain iron deficiency by postnatal day (P)15. Our dietary model allowed us to observe changes during ID at P15 and P30 and also after iron repletion at P70. Dendritic changes have been demonstrated with MAP-2 staining, but this stain only allowed for measurement of the first portion of the apical dendrite. Therefore, the Golgi stain was used to allow for tracing of the entire apical dendritic trees, with quantification using Sholl analysis to observe the growth trajectory. The objective was to determine how apical dendrite growth is altered, short term and long term, by early iron deficiency. Approximately 20 neurons were traced from each of the three time points and two dietary conditions. Four or more animals were used from each group. Results show early iron deficiency altered dendritic developmental trajectory. Distance to peak branching was shorter in the ID and formerly ID animals as well as thinner third generation branches at P15. Also at P70 in FID animals, peak branching density was decreased. Decreased transcript levels were seen in the IDA and formerly IDA animals. Altered transcript levels of various cytoplasmic and transmembrane proteins critical to structural growth (RhoA, Rac1, Cdc42, Cypin, Cofillin, Profilin, Crmp1, Cxcr4) support altered morphology and contribute to reduced plasticity of the system. Early iron deficiency affects apical dendrite development and results in long term decreased cytoskeletal plasticity, these findings may underlie some of the functional deficits seen in this condition.