Iron Injection Restores Brain Iron and Hemoglobin Deficits in Perinatal Copper-Deficient Rats

Abstract

Copper (Cu) deficiency during perinatal development in rats is associated with anemia, lower plasma iron (Fe), and brain Fe. Experiments were conducted to inject Fe dextran into Cu-deficient (Cu-) rat pups to attempt to reverse these conditions. Previous work with older Cu- rats did not reverse anemia following Fe injection. Dams began Cu-adequate (Cu+) or Cu- dietary treatments starting at embryonic d 7 and lasting through weaning. In Expt. 1, pups from each dietary treatment were given a single dose of Fe, 20 mg Fe/kg, or saline (S) at postnatal d 11 (P11). Plasma Fe and hemoglobin were higher in the Fe-injected groups at P13. Brain Fe deficit and brain transferrin receptor enhancement were eliminated in the Cu- group injected with Fe compared with Cu-S pups, supporting an association between low plasma Fe and low brain Fe. In Expt. 2, Fe treatment was increased to 45 mg Fe/kg. Four injections were given between P5 and P18 (total dose, 5-7 mg Fe). At P20, Fe concentrations in 4 brain regions (cortex, cerebellum, medulla/pons, and hypothalamus) generally were higher in all groups than in Cu-S pups. At P25, impaired vibrissae-elicited foot placement was evident in Cu-S rats and was not improved by Fe injection. However, at P26, the brain Fe deficit in Cu-S pups was eliminated by Fe injection. Fe injections in Cu- pups raised plasma Fe, brain Fe, and hemoglobin but did not reverse low cytochrome c oxidase or abnormal striatal behavior.

Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations

“…Cu deficiency increases liver Fe content and decreases serum and brain Fe levels (this study and Refs. 23,27). Fe deficiency also affects Cu homeostasis as evidenced by increased liver and brain Cu content in FeD rat dams and neonates (this study and Refs.…”

“…Our previous work demonstrated that perinatal Cu deficiency reduces neonatal brain Fe content and concomitantly increases brain TfR protein levels (23,27). In the current study, brain Fe content in P12 CuD pups trended downward, but brain TfR protein lev-els were not increased (Figs.…”

“…A 25 g aliquot of protein was subjected to SDS-PAGE on either a 15% gel [subunit IV of CCO (COX IV), Cu chaperone for superoxide dismutase (CCS), or lactate dehyrogenase, (LDH)] or a 8% gel [transferrin receptor 1 (TfR)]. Description of the transfer, reagents used for incubation, antibodies used, and techniques of detection are described elsewhere (27). LDH protein levels were assessed for both the 15 and 8% gels as loading controls.…”

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

“…41 Copper is known to regulate iron utilization in the bone marrow and in hemoglobin synthesis. [42][43][44][45] Importantly, both ABCB7 and ATP7A genes are expressed in the bone marrow 26,46 and in various tissues (Illumina Human Body Map 2.0), 26,46,47 (Supplementary Figure 5). Given the mutual regulatory influence of the copper and iron uptake, the clinical phenotype described in the Buryat patients may depend on presumable interaction of genetic defects in two genes for the MBPs in some tissue cells, an interesting case of syndrome inherited as a X-linked monogenic trait.…”

Effect of calcium-fortified milk-rich diets (either goat’s or cow’s milk) on copper bioavailability in iron-deficient anemia

“…Indeed, the Cu-dependent intestinal ferroxidase hephaestin is required for Fe absorption (Chen et al 2004). Moreover, Cu deficiency has been associated with lower plasma and brain concentrations of Fe, and impaired enterocyte Fe transfer due to decreased hephaestin activity which further lowers plasma Fe and leads to Fe deficiency (Pyatskowit and Prohaska 2008).…”