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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron deficiency (ID) in early life alters the course of behavioral and cognitive development in humans, causing decreased physical activity and responsiveness to the environment. The effects of ID on behavior are similar in rats and hypothesized to be related to ID-related impairments in central dopamine pathways. The objective of this study was to examine the association between brain iron measures of dopamine function, and behavioral measures of activity and reactivity. Male and female weanling rats were fed either an iron deficient diet or control diet for 6 weeks. The iron deficient rats showed significantly decreased activity and increased anxiety-like behaviors. Iron deficient rats also showed significant decrements in brain iron content in the corpus striatum, prefrontal cortex, and midbrain and decreases in dopamine receptors and the transporter in the same areas. Multiple regression analysis showed ventral midbrain iron concentration and dopamine D(1) receptor density to be highly associated with exploration and repeated movements, respectively. In addition, the results showed anxiety-like behaviors to be related to prefrontal cortex dopamine transporter and dopamine D(1) receptor densities. We conclude from these analyses that iron concentration in dopamine containing regions and densities of dopamine receptors and the transporter, are significant predictors of measures of activity and reactivity. These observations also strengthen the argument that the Fe-dopamine link is fundamental to understanding biobehavioral difficulties seen in children with ID anemia.
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PMID:Neurobehavioral analysis of developmental iron deficiency in rats. 1219 38

Iron deficiency impairs nigrostriatal and mesolimbic dopamine systems by causing decreased densities of D(1) and D(2) receptors and the dopamine transporter in the terminal fields, caudate-putamen and nucleus accumbens. Iron deficiency also causes deficits in dopamine-related pharmacological indices, e.g., deficits in locomotor stimulation by cocaine and locomotor inhibition by raclopride. Based on this knowledge, we hypothesized that iron deficiency would have a major impact on cocaine self-administration. Male Sprague-Dawley rats were fed an iron-deficient diet starting at weaning (Day 21) and continuing throughout the experiment. At 57-58 days of age, all animals had catheters implanted surgically into the jugular vein. Approximately 2 weeks later, all animals were trained to lick an empty spout for intravenous cocaine, delivered by infusion pump at 0.33 mg/kg. During the course of training, all animals acquired intravenous cocaine self-administration, however, the course of acquisition was significantly slower for the iron-deficient animals. When tested for responding on a progressive ratio (PR) schedule, the control animals maintained a constant number of infusions, whereas the responding of the iron-deficient animals fell off sharply. When the dose of cocaine was decreased, control, but not iron-deficient adjusted the amount administered by increasing the number of infusions. Finally, the failure to respond by the iron-deficient animals was not simply due to a failure to lick (i.e., a motor impairment), because both the iron-deficient and the control animals emitted approximately 1000 licks/20 min session when given free access to a palatable 0.1 M sucrose solution. Taken together, the data show that severe iron deficiency early in life can diminish the capacity of cocaine, but not sucrose to reinforce behavior. The question raised by this research thus, is whether iron deficiency alters hedonic-like responses only to dopamine-related behaviors and the degree to which willingness to "work" contributes to the effect.
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PMID:Iron deficiency in rats decreases acquisition of and suppresses responding for cocaine. 1221 26

Therapy-related augmentation of the symptoms of restless legs syndrome (RLS) is an important clinical problem reported in up to 60% of patients treated with levodopa and, to a lesser extent, with dopamine agonists. The efficacy of low-dose dopaminergic drugs for RLS has been established, but the mode of action is unknown. Here, we review the existing data and conclude that augmentation is a syndrome characterised by a severely increased dopamine concentration in the CNS; overstimulation of the dopamine D1 receptors compared with D2 receptors in the spinal cord may lead to D1-related pain and generate periodic limb movements; iron deficiency may be a main predisposing factor of augmentation, probably caused by a reduced function of the dopamine transporter; therapy with levodopa or dopamine agonists should remain at low doses and; iron supplementation and opiates are the therapy of choice to counter augmentation.
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PMID:Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome. 1698 35

Delusional parasitosis (DP) is a psychotic condition in which a person has the unshakeable and mistaken belief (delusion) and/or aberrant perception (hallucination) of being infested with parasites. The disorder will be usually classified in a primary DP-group without a detectable cause (so-called pure forms), while secondary DP-groups are associated with general organic conditions, psychiatric illnesses and drugs (substance induced). Etiology and pathophysiology of DP remain however unknown. In the present paper we hypothesize for the first time a decreased striatal dopamine transporter (DAT)-functioning (corresponding with an increased extracellular dopamine-level) as etiologic condition for DP (primary and secondary groups). The DAT as key regulator of the dopamine-reuptake in the human brain is well known (regulation of the extracellular dopamine concentration). It is a presynaptic plasma membrane protein highly dense represented in the striatum. The hypothesis of a decreased DAT-functioning as etiologic condition by DP is revealed in case reports which show that DAT-inhibitors, such as cocaine, pemoline, methylphenidate and other amphetamine-derivatives can induce the clinical expression of DP. Several other associated causes of secondary DP-groups (medications, parkinson, chorea huntington, multiple system atrophy, diabetes, cerebrovascular diseases, alcoholism, traumatic brain injury, hyperuricemia, human immunodeficiency virus, iron deficiency, schizophrenia, depression) suggest that the clinical expression of DP may be related to a decreased striatal DAT-functioning (blocking, reduced ligand binding, reduced density, reduced activity). Our examined DP-cases (2-females) show means of magnetic resonance imaging a structurally damaged striatum. Furthermore, we presume that by the primary DP-group, the physiologically age-related decline of the DAT-density is pathologically elevated. Based on this hypothesis we show in the present paper the relation between DP and decreased striatal DAT-functioning, trying to give a new insight into the pathophysiologically mechanism involved. The hypothesis provides supporting evidence that increased levels of extracellular dopamine in the striatum of DP-patients is likely to be the result of decreased DAT-functioning and not increased rates of release. The hypothesis can be investigated simply by dopamine transporter imaging in patients with DP.
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PMID:Delusional parasitosis and the dopamine transporter. A new insight of etiology? 1713 47

Neurological development and functioning of dopamine (DA) neurotransmission is adversely affected by iron deficiency in early life. Iron-deficient rats demonstrate significant elevations in extracellular DA and a reduction in dopamine transporter (DAT) densities in the caudate putamen and nucleus accumbens. To explore possible mechanisms by which cellular iron concentrations control DAT functioning, endogenous DAT-expressing PC12 cells were used to determine the effect of iron chelation on DAT protein and mRNA expression patterns. In addition, we used human DAT (hDAT)-transfected Neuro2a (N2A) cells to examine DAT degradation and trafficking patterns. A 50 microM treatment for 24 h with the iron chelator, desferrioxamine (DFO), significantly decreased dopamine uptake in a dose-dependent manner, with no apparent change in K(m), in both PC12 and N2A cells. Reduced DA uptake was accompanied by concentration- and time-dependent reductions in total DAT protein levels in both cell lines. Exposure to increasing concentrations of DFO did not significantly alter DAT mRNA in either PC12 or N2A cells. However, DAT degradation rates increased three-fivefold in both cell types exposed to 50 microM DFO for 24 h. Biotinylation studies in N2A cells indicate a more dramatic loss of DAT in the membrane fraction, while OptiPrep fractionation experiments revealed an increase in lysosomal DAT with iron chelation. Inhibition of protein kinase C activation with staurosporin prevented the effect of iron chelation on DAT function, suggesting that in vitro iron chelation affects DAT primarily through the effects on trafficking rather than on synthesis.
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PMID:Down-regulation of dopamine transporter by iron chelation in vitro is mediated by altered trafficking, not synthesis. 1722 37

Thy-1, a glycosyl-phosphatidylinositol (GPI)-linked integral membrane protein, may play a role in stabilizing synapses. Thy1 was identified in a gene expression analysis as iron responsive, and subsequent cell culture and animal models of iron deficiency expanded this finding to the protein. The importance of Thy1 in influencing neurotransmitter feedback mechanisms led to this study to determine the relative effects of Thy1 deficiency and dietary iron deficiency on the dopaminergic system in the mouse striatum. The model for this analysis was the Thy1 null mutant mouse in the presence or absence of dietary iron deficiency. The results revealed significant differences in dopaminergic profiles associated with Thy1 and iron deficiency and also a sex effect. For example, both iron deficiency and the absence of Thy1 are associated with increased dopamine in both sexes, but the dopamine transporter is increased in these experimental groups only in female mice. In male mice, the increase in dopamine transporter is found only in the Thy1 null mutants. Increases in vesicular monoamine transporter and phosphorylated tyrosine hydroxlyase are found only in iron-deficient mice. In contrast decreased release of dopamine from synaptosomes is found only in the Thy1 null mutant animals. In general, these results indicate that a loss of Thy1 can influence the dopaminergic profile in the striatum. Furthermore, the results reveal consistent differences in the dopaminergic profile in Thy1 knockout mice compared with iron-deficient mice, indicating that the effects of iron deficiency are not due only to a change in Thy1 expression.
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PMID:Comparative study of the influence of Thy1 deficiency and dietary iron deficiency on dopaminergic profiles in the mouse striatum. 1861 41

Monoamine metabolism in the central nervous system is altered by dietary iron deficiency, with a stronger effect seen during the active than rest span of the circadian cycle. In this report, we examined changes in intracellular and extracellular monoamine levels, synthetic enzymes, transporter and receptor densities, and responses to amphetamine-induced dopamine (DA) efflux in iron-deficient and iron-sufficient mice. Extracellular striatal DA levels were 15-20% higher in all groups during the active dark phase compared to the inactive light phase, with correspondingly lower dopamine transporter (DAT) and higher tyrosine hydroxylase levels. Iron deficiency decreased DAT density by 20% and 28% in the light and dark phases, respectively, and elevated the DOPAC/DA ratio only in the dark, indicating that iron deficiency does interact with the normal diurnal cues for cyclicity. Enhanced DA efflux after amphetamine stimulation indicates no limitation on monoamine synthesis and release and is consistent with altered synaptic efficacy and perhaps recycling of DA in iron deficiency. These experimental findings provide new evidence that brain iron insufficiency does have a differential effect on the DA system at different biological times of the day and night and may be causally related to the phasic motor symptoms observed in Restless Legs Syndrome.
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PMID:Iron deficiency alters the day-night variation in monoamine levels in mice. 1936 Apr 89

Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI). Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2) for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2). Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT) and dopamine receptor D(1) (D1R) levels were reduced and dopamine receptor D(2) (D2R) levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.
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PMID:Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency. 2247 10