Iron deficiency and manganese exposure are associated with decreases in neurotransmitter uptake

Iron deficiency (ID) is a common nutritional problem throughout the world and is associated with cognitive and behavioral problems. Data suggest that perturbations in dopamine (DA) biology may drive these problems and more recently norepinephrine (NE) and serotonin (5HT) have been implicated. A possible mechanism in which ID causes a disturbance in neurochemistry is by facilitating brain manganese (Mn) accumulation. The goal of this study was to examine the effect of dietary ID and subsequent Mn accumulation on DA, NE, and 5‐HT uptake in rats. Sprague‐Dawley rats were randomly placed into one of four dietary groups: control or iron‐deficient, with or without additional Mn. At four, five, and six weeks, synaptosomes were isolated from the striatum (STR), locus ceruleus (LC), and cerebellum (CB) and utilized to assess neurotransmitter uptake. Synaptosomal iron (Fe) concentration was associated with decreased uptake of DA, 5‐HT and NE in the STR at six weeks (p<0.05), while Mn concentration was inversely correlated with NE uptake in the LC at six weeks (R=−0.753, p=0.001). These data demonstrate that Fe and Mn are inversely related in terms of neurochemistry (i.e., low Fe and high Mn associated with attenuated NE uptake) and this effect is brain region dependent. Supported by NIEHS # ES013791 ‐01.