Iron deficiency decreases dopamine D1 and D2 receptors in rat brain

Abstract

Iron deficiency (ID) in early life is known to alter neurological development and functioning, but data regarding specific effects on dopamine biology are lacking. The objective of this study was to determine the extent of functional alterations in dopamine receptors in two dopaminergic tracts in young, growing, iron-deficient rats. Forty male and 40 female weanling Sprague-Dawley rats were fed either an iron-deficient (ID) diet or control (CN) diet for 6 weeks. ID decreased densities of D(1) and D(2) receptors in the caudate-putamen and decreased D(2) receptor densities in the nucleus accumbens. There were no apparent effects of ID on the affinities for the ligands in either receptor in several brain regions. In situ hybridization studies for both dopamine receptors revealed no significant effect of ID on mRNA expression for either receptor. Iron-deficient rats had a significantly higher ED(50) for raclopride-induced hypolocomotion in male and female rats compared to control rats of each sex. The loss of iron in the striatum due to dietary ID was significantly correlated with the decrease in D(2) receptor density; however, this relationship was not apparent in other brain regions. These experiments thus demonstrate abnormal dopamine receptor density and functioning in several brain regions that are related to brain regional iron loss. Importantly, the impact of ID on dopamine was more pronounced in males than females, demonstrating sex-related different sensitivities to nutrient deprivation.

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-…”

Consequences of iron depletion on health in menstruating women

“…Among these, surprisingly, memory disorders appeared as significantly less frequent in women with serum ferritin concentrations below 15 mg/l, or even more so, below 10 mg/l. Others demonstrated that, in rodents, iron deficiency without anemia protected against the neurodegeneration of specific cerebral zones, in particular, the hippocampus zone (Hallberg & Asp, 1996), one of the memory zones (Bohbot et al, 2000), whereas subjects with iron-deficient anemia presented more frequently with memory loss because of major alterations of enzymatic reactions of the serotonin metabolism (mitochondrial aldehyde oxidase) or of catecholamines catabolism (mitochondrial monoamine oxidase) within the neuronal mitochondria, leading to a cerebral storage of triptaminergic derivatives and of catecholamines (adrenaline, noradrenaline and dopamine) (Youdim et al, 1983(Youdim et al, , 1989Hallberg & Asp, 1996;Youdim & Yehuda, 2000;Erikson et al, 2001). …”

Iron deficiency anemia from diagnosis to treatment in children

“…The mechanism of action by which iron deficiency causes to neurocognitive disorders is not fully understood. In some studies, it was shown that ID decreased expression of dopamin receptors, disrupted myelinization or disrupted the function of various enzymes involved in the nerve tissue (17)(18)(19). Again, another important yet controversial clinical effect of iron deficieny is its effects on the immune system (20)(21)(22).…”