Brain iron: a lesson from animal models

Abstract

Brain and blood iron deficiency (ID) can be nutritionally induced. Significant behavioral and brain-biochemical changes are observed in rats rendered iron deficient, including complete reversal of the circadian cycles of motor activity, changes in thermoregulation and stereotyped behavior, and an increased pain threshold. The increase in pain threshold is affected by diurnal factors and peripheral treatment with beta-endorphin has a significant analgesic effect, implicating selective changes in the blood-brain barrier. These effects along with modifications in responses to dopaminergic drugs, interactions of ID with neuroleptic drugs, and modifications in behavior as a result of selective brain lesions, lead to two conclusions: this animal model is appropriate for human anemia and the best explanation for the variety of behavioral and brain biochemical changes in ID rats is that the principal effect of brain ID is a selective decrease in the functional level of the dopaminergic D2 system.

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial

“…[23][24][25] The effects of iron deficiency on fatigue can be explained by decreased activity of irondependent enzymes; for example, those affecting the metabolism of neurotransmitters that enhance neurophysiologic changes. [26][27][28][29] However, we presume that such physiologic changes could be confused with depression or anxiety; thus, the effect of iron supplementation on mood disor-…”

Iron Status and Neurobehavioral Development of Premature Infants

“…Earlier rodent studies documented the effect of decrease in brain iron on a variety of dopaminergic functions and dopamine-mediated behaviors, especially, when iron deficiency occurs early in life. [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.…”

Prävalenz und Risikofaktoren von Eisenmangel bei jungen Müttern*

“…Diese Testergebnisse konnten durch Eisensupplementierung verbessert werden (Idjradinata and Pollitt, 1993). Die Ursache für diesen Zusammenhang wird darin gesucht, daß bei Eisenmangel die Monoaminooxidase vermindert und die Funktion von D ¾ -(Dopamin)Rezeptoren reduziert ist, was die Reizübertragung möglicherweise stört und somit zu kognitiven Störungen führt (Yehuda and Youdim, 1989). …”