Iron deficiency alters monoamine catabolism as well as feedback regulation of DA transporter functioning

Abstract

Iron deficiency (ID) causes decreased dopamine (DA) D2 receptor density, decreased DA transporter (DAT) density and alters DA signaling in the brain. We found that post weaning ID results in a 61% decrease in MAO-B activity in striatum. No effect was seen on MAO-A or COMT activity. Direct infusion of 1 μM FeSO4 was found to rescue this deficit indicating iron is vital for proper catecholamine metabolism. We further explored iron’s role on the catecholamine system by using in vivo microdialysis and no net flux. We found that ID increases extracellular dopamine by 26% and decreases extraction fraction (Ed) by 20% implying the DAT function is decreased by ID. Furthermore, stimulation of the D2 system by infusion of 5 μM quinpirole during NNF results in a decrease in basal extracellular DA for both control (CN) and ID animals indicating that the feedback regulation of synthesis and release is intact, although D2 density is decreased. Additionally, quinpirole infusion increased Ed by 45% in CN animals, however there was no change in ID Ed. This lack of response indicates disruption in the signal pathway regulating DAT functionality. Infusion of 1 μM FeSO4 was not able to correct this.