scholarly journals Iron Deficiency and Iron Excess Differently Affect Dendritic Architecture of Pyramidal Neurons in the Hippocampus of Piglets

2020 ◽  
Vol 151 (1) ◽  
pp. 235-244
Author(s):  
Vivian Perng ◽  
Chong Li ◽  
Carolyn R Klocke ◽  
Shya E Navazesh ◽  
Danna K Pinneles ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Hippocampal Neurons ◽  
Iron Homeostasis ◽  
Pyramidal Neurons ◽  
Iron Status ◽  
Duodenal Mucosa ◽  
Deficiency Anemia ◽  
Final Body Weight ◽  
Iron Regulatory Proteins ◽  
Dendritic Complexity

ABSTRACT Background Both iron deficiency and overload may adversely affect neurodevelopment. Objectives The study assessed how changes in early-life iron status affect iron homeostasis and cytoarchitecture of hippocampal neurons in a piglet model. Methods On postnatal day (PD) 1, 30 Hampshire × Yorkshire crossbreed piglets (n = 15/sex) were stratified by sex and litter and randomly assigned to experimental groups receiving low (L-Fe), adequate (A-Fe), or high (H-Fe) levels of iron supplement during the pre- (PD1–21) and postweaning periods (PD22–35). Pigs in the L-Fe, A-Fe, and H-Fe groups orally received 0, 1, and 30 mg Fe · kg weight−1 · d−1 preweaning and were fed a diet containing 30, 125, and 1000 mg Fe/kg postweaning, respectively. Heme indexes were analyzed weekly, and gene and protein expressions of iron regulatory proteins in duodenal mucosa, liver, and hippocampus were analyzed through qRT-PCR and western blot, respectively, on PD35. Hippocampal neurons stained using the Golgi-Cox method were traced and their dendritic arbors reconstructed in 3-D using Neurolucida. Dendritic complexity was quantified using Sholl and branch order analyses. Results Pigs in the L-Fe group developed iron deficiency anemia (hemoglobin = 8.2 g/dL, hematocrit = 20.1%) on PD35 and became stunted during week 5 with lower final body weight than H-Fe group pigs (6.6 compared with 9.6 kg, P < 0.05). In comparison with A-Fe, H-Fe increased hippocampal ferritin expression by 38% and L-Fe decreased its expression by 52% (P < 0.05), suggesting altered hippocampal iron stores. Pigs in the H-Fe group had greater dendritic complexity in CA1/3 pyramidal neurons than L-Fe group pigs as shown by more dendritic intersections with Sholl rings (P ≤ 0.04) and a greater number of dendrites (P ≤ 0.016). Conclusions In piglets, the developing hippocampus is susceptible to perturbations by dietary iron, with deficiency and overload differentially affecting dendritic arborization.

scholarly journals Molecular Mechanisms Regulating Hepcidin Revealed by Hepcidin Disorders

2011 ◽  
Vol 11 ◽  
pp. 1357-1366 ◽  
Author(s):  
Clara Camaschella ◽  
Laura Silvestri
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Transcriptional Control ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Human Life ◽  
Genetic Diseases ◽  
The Body ◽  
Deficiency Anemia ◽  
Iron Regulatory Proteins

Iron is essential for human life, but toxic if present in excess. To avoid iron overload and maintain iron homeostasis, all cells are able to regulate their iron content through the post-transcriptional control of iron genes operated by the cytosolic iron regulatory proteins that interact with iron responsive elements on iron gene mRNA. At the systemic level, iron homeostasis is regulated by the liver peptide hepcidin. Disruption of these regulatory loops leads to genetic diseases characterized by iron deficiency (iron-refractory iron-deficiency anemia) or iron overload (hemochromatosis). Alterations of the same systems are also found in acquired disorders, such as iron-loading anemias characterized by ineffective erythropoiesis and anemia of chronic diseases (ACD) associated with common inflammatory conditions. In ACD, iron is present in the body, but maldistributed, being deficient for erythropoiesis, but sequestered in macrophages. Studies of the hepcidin regulation by iron and inflammatory cytokines are revealing new pathways that might become targets of new therapeutic intervention in iron disorders.

scholarly journals Iron Deficiency and Iron Excess Alter Dendritic Architecture of Pyramidal Neurons in the Hippocampus of Neonatal Pigs

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1232-1232
Author(s):  
Vivian Perng ◽  
Chong Li ◽  
Shya Navazesh ◽  
Carolyn Klocke ◽  
Danna Pinneles ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Iron Homeostasis ◽  
Pyramidal Neurons ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Dendritic Arborization ◽  
Sholl Analysis ◽  
Iron Deficient ◽  
Gene And Protein Expression ◽  
Significant Difference

Abstract Objectives The study assessed effect of dietary iron on iron homeostasis and dendritic architecture of hippocampal neurons in young piglets. Methods On postnatal day (PD) 1, 30 piglets (15 male/female) were blocked by sex and randomized to treatments by receiving no (N), low (L) or high (H) dose of iron supplement during pre- (PD1–21) and post-weaning period (PD22–35). Pigs in N, L, and H group orally received 0, 1, and 30 mg iron/(kg BW· d) as ferrous sulfate solution pre-weaning and were fed a solid diet containing 30, 125, and 1000 mg iron/kg post-weaning, respectively. Blood samples were collected on PD1 and weekly thereafter to analyze iron biomarkers. Iron homeostasis in hippocampus was assessed by measuring gene and protein expression of iron transporters. Hippocampal neurons stained with Golgi-Cox method were traced and 3D reconstructed using Neurolucida. Dendritic arborization were quantified through Sholl analysis and Neurolucida Explorer. Results Pigs in H group had the highest growth rate, whereas N pigs displayed growth retardation from PD27 to PD35, resulting in significant difference in body weight compared to H group (P < 0.05). Iron dose-dependently increased hemoglobin (Hb), hematocrit, plasma iron and transferrin saturation since PD7 or PD14 (P < 0.05). Pigs in N group became iron deficient since PD14 (Hb < 11 g/dL). Similarly, hippocampal ferritin expression was upregulated with the increase of iron (P < 0.05). The mRNA expression of TFRC and DMT1 in hippocampus was highest in N and lowest in H group (P < 0.05). Despite relatively low abundance, HAMP expression tended to be higher in H than that in N (P < 0.10). Sholl analysis uncovered significant main effect of treatment on basilar dendritic arborization of CA1 and CA3 pyramidal neurons (P ≤ 0.04). There were less branching nodes and dendrites in N than in H group (P < 0.05). However, the difference in dendritic arborization was primarily derived from the higher order (> 3) of branches in both regions. Iron supplementation did not affect architecture of apical dendrites of granule cells in dentate gyrus. Conclusions Early-life iron status affects hippocampal iron homeostasis and alters development of pyramidal neurons in a piglet model. Funding Sources NIFA Hatch/Multistate Research Fund.

scholarly journals Interrelationships between tissue iron status and erythropoiesis during postweaning development following neonatal iron deficiency in rats

2011 ◽  
Vol 300 (3) ◽  
pp. G470-G476 ◽  
Author(s):  
Narasimha V. Hegde ◽  
Erica L. Unger ◽  
Gordon L. Jensen ◽  
Pamela A. Hankey ◽  
Robert F. Paulson
Keyword(s):  
Iron Deficiency ◽  
Iron Homeostasis ◽  
Iron Status ◽  
Dietary Iron ◽  
Altered Expression ◽  
Iron Regulatory Proteins ◽  
Adequate Diet ◽  
Stage Of Development ◽  
Tissue Iron ◽  
Neonatal Iron Deficiency

Dietary iron is particularly critical during periods of rapid growth such as in neonatal development. Human and rodent studies have indicated that iron deficiency or excess during this critical stage of development can have significant long- and short-term consequences. Since the requirement for iron changes during development, the availability of adequate iron is critical for the differentiation and maturation of individual organs participating in iron homeostasis. We have examined in rats the effects of dietary iron supplement following neonatal iron deficiency on tissue iron status in relation to erythropoietic ability during 16 wk of postweaning development. This physiological model indicates that postweaning iron-adequate diet following neonatal iron deficiency adversely affects erythroid differentiation in the bone marrow and promotes splenic erythropoiesis leading to splenomegaly and erythrocytosis. This altered physiology of iron homeostasis during postweaning development is also reflected in the inability to maintain liver and spleen iron concentrations and the altered expression of iron regulatory proteins in the liver. These studies provide critical insights into the consequences of neonatal iron deficiency and the dietary iron-induced cellular signals affecting iron homeostasis during early development.

scholarly journals Effect of Daily Iron Supplementation on Infantile Iron Homeostasis in Preterm Infants

2021 ◽  
Vol 9 ◽  
Author(s):  
Mingyan Li ◽  
Ying Lv ◽  
Jionghuan Ying ◽  
Lin Xu ◽  
Weijun Chen ◽  
...  
Keyword(s):  
Side Effects ◽  
Iron Deficiency ◽  
Blood Transfusion ◽  
Preterm Infants ◽  
Early Treatment ◽  
Iron Supplementation ◽  
Iron Homeostasis ◽  
Iron Status ◽  
Deficiency Anemia ◽  
Factors Affecting

Objective: The aim of this study was to investigate the effects of unified iron supplementation and identify the factors related to the iron homeostasis among preterm infants.Method: A total of 250 preterm infants were divided into neonatal anemic (NA, n = 154) and non-neonatal anemic group (NNA, n = 96). Iron supplements at a dose of 2 mg/kg per day were given from 40 weeks' gestational age to 6 months. Iron status parameters were measured at 3 and 6 months, respectively. Prevalence of iron deficiency (ID) and iron deficiency anemia (IDA), and the correlated factors were analyzed. Growth and side-effects were monitored.Results: There were no significant differences for the prevalence of ID or IDA between the two groups. Multivariate regression analyses showed that higher Hb at birth and early treatment of blood transfusion reduced the risk of ID/IDA at 3 months (all p < 0.05); while higher level of Hb at 3 months (p = 0.004) and formula feeding reduced the occurrence of ID/IDA at 6 months (p < 0.05); males had a 3.35 times higher risk to develop ID/IDA than girls (p = 0.021). No differences in growth and side effects were found.Conclusion: A daily dose of 2 mg/kg iron supplement is beneficial to maintain iron homeostasis in majority preterm infants within 6 months regardless of their neonatal anemia history. Under the routine iron supplementation, Hb level at birth and at 3 months, early treatment of blood transfusion, gender and feeding patterns are the major factors affecting the prevalence of ID/IDA among preterm infants in infancy.

scholarly journals Iron-Containing Contraceptives and Their Effect on Hemoglobin and Biomarkers of Iron Status: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2340
Author(s):  
Jordie A. J. Fischer ◽  
Carolina S. Sasai ◽  
Crystal D. Karakochuk
Keyword(s):  
Oral Contraceptive ◽  
Iron Deficiency ◽  
Contraceptive Use ◽  
Iron Status ◽  
Cost Effective ◽  
Narrative Review ◽  
Deficiency Anemia ◽  
Oral Contraceptive Use ◽  
Contraception Use ◽  
Hb Concentration

Oral contraceptive use has been associated with decreased menstrual blood losses; thus, can independently reduce the risk of anemia and iron deficiency in women. Manufacturers have recently started to include supplemental iron in the non-hormonal placebo tablets of some contraceptives. The aims of this narrative review are: (i) to describe the relationship between oral contraceptive use and both anemia and iron status in women; (ii) to describe the current formulations of iron-containing oral contraceptives (ICOC) available on the market; and (iii) to systematically review the existing literature on the effect of ICOC on biomarkers of anemia and iron status in women. We discovered 21 brands of ICOC, most commonly including 25 mg elemental iron as ferrous fumarate, for seven days, per monthly tablet package. Our search identified one randomized trial evaluating the effectiveness of ICOC use compared to two non-ICOC on increasing hemoglobin (Hb) and iron status biomarker concentrations in women; whereafter 12 months of contraception use, there were no significant differences in Hb concentration nor markers of iron status between the groups. ICOC has the potential to be a cost-effective solution to address both family planning needs and iron deficiency anemia. Yet, more rigorous trials evaluating the effectiveness of ICOC on improving markers of anemia and iron deficiency, as well as investigating the safety of its consumption among iron-replete populations, are warranted.

scholarly journals Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and Mnemonic Functioning in Women in a Randomized Controlled Trial in India

2017 ◽  
Vol 147 (12) ◽  
pp. 2297-2308 ◽  
Author(s):  
Michael J Wenger ◽  
Laura E Murray-Kolb ◽  
Julie EH Nevins ◽  
Sudha Venkatramanan ◽  
Gregory A Reinhart ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Status ◽  
Controlled Trial ◽  
Reproductive Age ◽  
Deficiency Anemia ◽  
Control Group ◽  
Attention And Memory ◽  
Double Blind ◽  
Iron Deficient ◽  
Mnemonic Function

Abstract Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory. Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function. Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18–55 y. Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function. Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

Iron Homeostasis and Disorders in Dogs and Cats: A Review

2011 ◽  
Vol 47 (3) ◽  
pp. 151-160 ◽  
Author(s):  
Jennifer L. McCown ◽  
Andrew J. Specht
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Diagnostic Testing ◽  
Clinical Manifestations ◽  
Essential Element ◽  
The Body ◽  
Deficiency Anemia ◽  
Enzyme Systems ◽  
Living Organisms

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.

scholarly journals Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

2018 ◽  
Vol 115 (12) ◽  
pp. 3000-3005 ◽  
Author(s):  
Benjamin H. Hudson ◽  
Andrew T. Hale ◽  
Ryan P. Irving ◽  
Shenglan Li ◽  
John D. York
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Reduction ◽  
Genetic Basis ◽  
Iron Homeostasis ◽  
Deficiency Anemia ◽  
Sulfur Assimilation ◽  
Nucleotide Hydrolysis ◽  
Evolutionarily Conserved ◽  
Organismal Development

Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis.

Fortification of tempeh with encapsulated iron improves iron status and gut microbiota composition in iron deficiency anemia condition

2018 ◽  
Vol 48 (6) ◽  
pp. 962-972 ◽  
Author(s):  
Rio Jati Kusuma ◽  
Aviria Ermamilia
Keyword(s):  
Iron Deficiency ◽  
Gut Microbiota ◽  
Iron Deficiency Anemia ◽  
Iron Status ◽  
Deficiency Anemia ◽  
Microbiota Composition ◽  
Iron Fortification ◽  
Iron Matrix ◽  
Content Type ◽  
Gut Microbiota Composition

Purpose Iron deficiency anemia (IDA) is one of the most major micronutrient deficiencies worldwide. Food fortification is one strategy for reducing IDA in the population despite concern regarding the gut pathogenic bacteria overgrowth. The purpose of this study was to evaluate the effect of iron encapsulation in banana peel matrix on iron status and gut microbiota composition in iron deficiency anemia. Design/methodology/approach Anemia was induced in 35 male Sprague Dawley rats of age two weeks by the administration of iron-free diet for two weeks. Rats then randomly divided into control, iron-fortified tempeh (temFe) dose 10 and 20 ppm, iron matrix-fortified tempeh dose 10 and 20 ppm and iron matrix fortified tempeh dose 10 and 20 ppm with probiotic mixture. Blood was drawn at Weeks 2 and 6 for hemoglobin and serum iron analysis. Rats were sacrificed at the end of Week 6, and cecal contents were collected for Lactobacillus, Bifidobacteria and Enterobactericeae analysis. Findings Hemoglobin and serum iron were significantly increased (p < 0.05) in all iron-fortified group with the highest value found in iron matrix dose 20 ppm (10.71 ± 0.15 g/dl and 335.83 ± 2.17 µg/dl, respectively). The cecal Lactobacillus and Bifidobacteria did not differ significantly between groups. Cecal Enterobactericeae was significantly different (p < 0.05) among groups with the lowest level in the temFe-20 (2.65 ± 0.78 log CFU) group. Research limitations/implications The use of commercial inoculum instead of pure Rhizopus oligosporus mold for developing the fortified tempeh may impact the effect of product on cecal gut microbiota composition, as different molds and lactic acid bacteria can grow in tempeh when using commercial inoculum. Social implications In Indonesia, iron fortification is conducted primarily in noodles and flour that limits the impact of iron fortification for reducing IDA in population. Iron fortification in food that was daily consumed by people, that is, tempeh, is potential strategy in reducing IDA in population. Originality/value Tempeh fortification using encapsulated iron improved iron status and gut microbiota composition in iron deficiency anemia.

scholarly journals Occurrence of neonatal diarrhea in calves with iron-deficiency anemia

2019 ◽  
Vol 73 (1) ◽  
pp. 1-9
Author(s):  
Radisa Prodanovic ◽  
Sreten Nedic ◽  
Oliver Radanovic ◽  
Vesna Milicevic ◽  
Ivan Vujanac ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Status ◽  
Enterotoxigenic Escherichia Coli ◽  
Deficiency Anemia ◽  
Fecal Samples ◽  
Gut Function ◽  
History Of ◽  
Neonatal Calves ◽  
Diarrheic Calves

Introduction. Neonatal calves are often deficient in iron. Accumulating evidence indicates that iron status is associated with disease pathologies including diarrhea. Our objective was to examine the association between iron status and gut function in neonatal calves with and without a history of calf diarrhea. Materials and Methods. Calves were divided into two groups based on their history of diarrhea; the first group were diarrheic calves (n=6) and the second group were non-diarrheic healthy calves (n=6). Blood samples (n=12) were collected at day 12 of age and erythrogram determination and measurements of serum iron and total iron binding capacity were performed. Hematological values were measured using an automatic analyzer, and biochemical properties were determined spectrophotometrically. Fecal samples were obtained from all calves and pH measured using semi quantitative test strips as well as being examined by bacterial cultivation for enterotoxigenic Escherichia coli, Salmonella spp. and Clostridium perfringens, by RT-PCR for the presence of bovine rotavirus, bovine coronavirus and bovine viral diarrhea virus, and by microscopy for the presence of Cryptosporidium parvum. Results and Conclusions. There were significant iron-related changes for most hematological indices in diarrheic calves; and iron (Fe) deficiency and microcytic, hypochromic anemia were diagnosed. The pH of the feces was significantly higher in diarrheic calves than in the non-diarrheic healthy group (P<0.01). All fecal samples were negative for the analyzed enteric pathogens. According to the results obtained, calves experiencing iron deficiency anemia exhibit changes in gut function leading to diarrhea as compared with a matched group of healthy calves.

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