PERINATAL IRON DEFICIENCY DECREASES CYTOCHROME OXIDASE (CytOx) ACTIVITY IN SPECIFIC REGIONS OF NEONATAL RAT BRAIN † 1721

Abstract

Brain iron deficiency bodes poorly for cognitive neurodevelopment and is present in newborns following gestations complicated by diabetes mellitus or intrauterine growth retardation. CytOx is an iron-containing enzyme involved in oxidative phosphorylation; its activity reflects neuronal metabolism. Regional CytOx activity has been mapped in the iron-sufficient adult rat brain but not in iron-sufficient or -deficient neonates. We hypothesized that neonatal brain iron deficiency alters regional CytOx activity. Pregnant Sprague-Dawley rats were fed iron-deficient or -sufficient chow from GD 1 until PND 7. CytOx activity in 14 brain nuclei (9 involved in memory pathways) was measured histochemically utilizing diaminobenzidine in frozen 15 μ coronal brain sections located approximately 2 mm posterior to the auditory meatus in 13 iron-deficient and 11 iron-sufficient pups. Quantitation of optical density (OD) was by Image-1. Brain iron concentration was 45% lower(p<0.001) with 13% less overall CytOx staining (p<0.001) in the iron-deficient group. CytOx activity loss in the iron- deficient group was not homogeneous; areas with reduced CytOx activity included the caudate/putamen(OD units: 94.8 ± 24.6 v 128.3 ± 33.1; p=0.02), the lateral amygdala (90.1 ± 17.3 v 119.3 ± 35.8; p=0.03) and the hippocampal CA1 region (151 ± 15 v 168 ± 15; p=0.05), while the cingulum, the medial and lateral habenula, and hippocampal areas CA3ab and CA3c of the hippocampus showed no loss. The piriform cortex, the lateral, ventral and dorsomedial thalamic nuclei, the periventricular arcuate hypothalamus and the dentate gyrus showed trends toward losses(p=0.06-0.19). The hippocampus is central to recognition memory circuits, the caudate-putamen and the piriform cortex to working/spatial memory circuits, and the amygdala and cingulum to emotional memory circuits. Perinatal iron deficiency has a non-homogeneous effect on neuronal metabolic activity, with certain nuclei involved in memory processing showing increased vulnerability. This factor may contribute to the poorer long-term developmental outcome observed among infants born following pregnancies complicated by gestational diabetes or intrauterine growth retardation. Supported by NICHD.