Iron Deficiency Alters Dopamine Transporter Functioning in Rat Striatum

Abstract

Iron deficiency anemia in early life produces profound changes in both in vivo and in vitro evaluations of dopamine (DA) functioning. This study employed both behavioral and biochemical approaches to examine the biological bases of alterations in striatal DA metabolism seen in iron-deficient rats. The purpose was to determine whether the DA transporter (DAT) was functionally altered in postweaning iron deficiency. Male and female 21-d-old Sprague-Dawley rats (n = 40) were fed either an iron-deficient (ID) diet (3 mg Fe/kg diet) or a control (CN) diet (35 mg Fe/kg diet) for 4 wk before behavioral testing. Motor activity responses to graded doses (3.75-30 mg/kg body) of the DA uptake inhibitor, cocaine, were significantly blunted in iron-deficient rats with a 50% higher half-maximal effective dose (ED(50)) in both males and females (CN-female, 7.1 +/- 0.9 mg/kg; ID-female, 11.2 +/-1.3 mg/kg; CN-male, 12.0 +/- 0.7 mg/kg; and ID-male, 17.0 +/- 1.8 mg/kg). Radioligand binding assays with (3)H-1-(2-(diphenylmethoxy)-ethyl)-4-(3-phenylpropyl) piperazine ((3)H-GBR12935) demonstrated that iron deficiency did not alter the affinity of the ligand for the DAT but did significantly decrease the density of the transporter by 30% in caudate putamen and 20% in nucleus accumbens. Iron deficiency also significantly decreased (3)H-DA uptake into striatal synaptosomes, but did not affect release of DA with potassium chloride stimulation. These experiments provide supporting evidence that elevated levels of extracellular DA in the striatum of iron-deficient rats is likely to be the result of decreased DAT functioning and not increased rates of release.

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

“…However, iron deficiency is known to alter dopamine transporter functioning (Erikson et al, 2000); so while we treated the ID rats with GBR identically to the rats fed the control diet, we did not see an effect of the drug on blocking the uptake of Mn into any brain region (data not shown). Iron (Fe) accumulated in a heterogeneous fashion across all brain regions.…”

Plasma iron levels appraised 15 days after spinal cord injury in a limb movement animal model

“…3 Iron-mediated impairment of tyrosine hydroxylase, which produces L-dopa that causes the decarboxylization of dopamine. 12 A reduction in the amount of ferritin in some regions of the brain causing a reduction in D1 and D2 dopamine receptors 13 and a subsequent deficiency in extracellular dopamine transport to the striatum. 12 Our study contradicts other studies such as that of Mizuno et al 14 that describe iron reduction in RLS individuals occurring only in the CNS with plasma iron concentrations remaining at normal values.…”

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.…”

“…Iron deficiency is considered one of the ten leading global risk factors in terms of its attributable disease burden. 4 There is an interconnectedness of iron-dependent changes in neurochemistry, 9 neurometabolism, and neuroanatomy during development, inducing changes in sensory/motor, cognitive/language, and social/emotion domains in iron-deficient people. 10 Iron is required for normal myelination and pathway transmission in the sensory systems may be affected by early iron deficiency.…”