Pre- and Postweaning Iron Deficiency Alters Myelination in Sprague-Dawley Rats

Abstract

Iron deficiency in early life is associated with hypomyelination; however, the role which iron plays in myelinogenesis is not clearly established. In this study, we examined the effect of preweaning [postnatal days (PND) 4–14 and PND 4–21] and postweaning (PND 21–63) iron deficiency on hindbrain 2′,3′-cyclic nucleotide 3′-phosphohydrolase (CNPase) activity (marker of oligodendrocyte metabolic activity) and myelin basic protein (MBP) concentrations. Both CNPase activity and concentrations in the cerebrum and hindbrain were significantly lower in pre- and postweaning iron-deficient rats. Similarly, MBP concentrations were also reduced (25–35%) in all three groups of iron-deficient animals. Iron-deficient animals also had significant alterations in the fatty acid composition of individual phospholipids within the hindbrain as well as changes in cytochrome oxidase activities. These studies show that postnatal iron deficiency, for as little as 10 days, can significantly alter the production of myelin and oligodendrocyte functioning. Importantly, postweaning iron deficiency was still associated with a decrease in CNPase activity and MBP concentrations despite occurring well past a likely key sensitive period of peak myelinogenesis at PND 8–12. This suggests that iron deficiency in later life, as well as during early postnatal growth, can effect the production and maintenance of myelin.

Effects of iron deficiency in infancy on patterns of motor development over time

“…Iron is involved in myelin production, and disruption in the availability of iron has been shown to impede myelination (Beard, Wiesinger, & Connor, 2003;Connor & Menzies, 1996;Ortiz et al, 2004). Specifically, ID during gestation and lactation in the rat is associated with changes in myelin components (protein, cholesterol, phospholipids and galactolipids) and compaction at adulthood despite an iron-sufficient diet since weaning (Ortiz et al, 2004).…”

Behavioral consequences of developmental iron deficiency in infant rhesus monkeys

“…In addition, diet-induced iron deprivation during development has been demonstrated to influence concurrent and subsequent behavioral performance in rodent models [4,17,37,53,67]. These rodent studies have also been able to begin describing how lack of iron influences brain development to produce the behavioral performance deficits [5,6,12,38].…”

Effectiveness of iron repletion in the diet for the optic nerve development of anaemic rats

“…37 A similar experimental regime has been used elsewhere. 9,55,56 Dietary iron deficiency results in a wide variety of structural and physiological defects 22,56,57 and a decrease in lipids and proteins on myelin. 6,13 Iron-deficient children were reported to have longer auditory brainstem response and visual-evoked potential latencies attributed to hypomyelination.…”

“…6,13 There are growing evidences that iron deficiency in early development affected brain myelination, 14,22,58 and some of them include a general decrease of its content and a differential composition of myelin. 14,57 The high levels of transferrin and iron in the after-birth period suggest that iron is extremely important to nervous system development for myelinization and development. Importantly, transferrin expression by oligodendrocytes is closely associated with the amount of myelin.…”

“…Importantly, transferrin expression by oligodendrocytes is closely associated with the amount of myelin. 57 The importance of iron in myelin production has been shown by studies showing that the decreased availability of iron in the diet is associated with hypomyelination. The timing of iron delivery to oligodendrocytes during development is also important because hypomyelination and the associated neurological sequelae persist long after the systemic iron deficiency has been corrected.…”