Iron Deficient and Manganese Supplemented Diets Alter Metals and Transporters in the Developing Rat Brain

Abstract

Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet. To assess the neurochemical interactions of dietary Fe deficiency and excess Mn during development, neonatal rats were exposed to either a control diet, a low-Fe diet (ID), or a low-Fe diet supplemented with Mn (IDMn) via maternal milk during the lactation period (postnatal days [PN] 4-21). In PN21 pups, both the ID and IDMn diets produced changes in blood parameters characteristic of Fe deficiency: decreased hemoglobin (Hb) and plasma Fe, increased plasma transferrin (Tf), and total iron binding capacity (TIBC). Treated ID and IDMn dams also had decreased Hb throughout lactation and ID dams had decreased plasma Fe and increased Tf and TIBC on PN21. Both ID and IDMn pups had decreased Fe and increased copper brain levels; in addition, IDMn pups also had increased brain levels of several other essential metals including Mn, chromium, zinc, cobalt, aluminum, molybdenum, and vanadium. Concurrent with altered concentrations of metals in the brain, transport proteins divalent metal transporter-1 and transferrin receptor were increased. No significant changes were determined for the neurotransmitters gamma aminobutyric acid and glutamate. The results of this study confirm that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn.

Manganese and its Role in Parkinson’s Disease: From Transport to Neuropathology

“…Mn exposure has been shown to affect tissue concentrations in a differential manner depending upon species and type of exposure. A significant increase in striatal GABA due to Mn exposure was found in rats (Garcia et al 2006(Garcia et al , 2007Gwiazda et al 2002); while a marginally significant (P < 0.1) decrease in pallidal GABA concentrations in monkeys exposed to airborne MnSO4 has been reported (Struve et al 2007); and no statistical difference was found in brain regional GABA concentrations in primates injected with Mn intravenously (Burton et al 2009). While tissue GABA concentrations can capture the overall status of GABA biology in an organism, it does not fully reflect the extracellular concentrations which are critical for neurotransmission.…”

“…It should be stressed that Fe deficiency affects about 2 billion subjects (Garcia et al 2007) and is a risk factor for Mn neurotoxicity even in absence of relevant exogenous exposures. Mn toxicity from various sources has been repeatedly reported in children (Fell et al 1996;Herrero Hernández et al 2003;Komaki et al 1999;Woolf et al 2002), including cognitive effects (Wasserman et al 2006).…”

Effects of customary drugs and modified herbal therapy on blood glucose and total antioxidant capacity in Streptozotocin induced diabetes in albino rats: A comparative analysis

“…Reports at some labs shows death rate as high as 50% at doses required to lower blood sugars [17]. Vanadium has been shown to cause death in both pregnant rats (45%) and fetuses [18]. In addition, different labs have produced different outcomes related to the blood sugars, with some labs finding little blood sugar lowering effect.…”

Effect of hemochromatosis on manganese neurotoxicity

“…Moreover, previous studies have shown that dysregulation of iron homeostasis can affect Mn metabolism and induce toxicity [102][103][104]. Iron-deficient animals have enhanced Mn absorption due to increased iron transporters expression [105,106].…”

“…Accumulating evidence has indicated that the absorption of Mn is altered by body iron status [103,168]. For example, iron deficient anemia increases intestinal absorption of Mn, whereas iron overload conditions decrease Mn uptake [107,169].…”