Effect of perinatal iron deficiency on myelination and associated behaviors in rat pups

Abstract

Iron deficiency in early development has been associated with irreversible alterations in brain myelination, but whether these neural changes are mirrored in altered behaviors in rats is not known. The goals were to determine if dietary induced gestational and lactational iron deficiency alters brain myelination and behaviors dependent on that system. Pregnant rats were randomly assigned to control (CN) or iron-deficient (ID) groups by providing iron-sufficient (40 ppm Fe) or iron-deficient (2-6 ppm Fe) diets from gestational day 5 through to weaning of pups. Thereafter, all offspring were fed the iron-sufficient diet. The myelination of subcortical white matter and the fimbria of hippocampus was measured by 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase, marker of oligodendrocyte) density at 25 days of age. Specific behavioral assessments were performed at multiple time points after birth. By contrast, ID rats had significantly lower density of CNPase in the subcortical white matter but the density of CNPase in fimbria of hippocampus was comparable to CN rats. Moreover, ID rats showed significant behavioral impairments in surface righting reflex, negative geotaxis reflex, vibrissae-evoked forelimb placing test and novel object recognition task. In conclusion, perinatal iron deficiency can significantly alter behavioral outcomes which may be due to delayed myelination in specific brain regions.