Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

Monika Burns, Sureshkumar Muthupalani, Zhongming Ge, Timothy C Wang, Vasudevan Bakthavatchalu, Catriona Cunningham, Kathleen Ennis, Michael Georgieff, James G Fox

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS1-infected INS-GAS mice will be an appropriate animal model for further study of the effects of concurrent H. pylori infection and anemia on iron homeostasis and adult iron-dependent brain gene expression.

Original languageEnglish
Pages (from-to)e0142630
JournalPloS ONE
Volume10
Issue number11
DOIs
Publication statusPublished - 17 Nov 2015

Keywords

  • Anemia/blood
  • Animals
  • Brain/metabolism
  • Brain-Derived Neurotrophic Factor/metabolism
  • Cell Size
  • Cytokines/genetics
  • Erythrocytes/physiology
  • Erythroid Cells/metabolism
  • Erythropoietin/blood
  • Ferritins/blood
  • Gastric Mucosa/metabolism
  • Gastritis/blood
  • Gene Expression
  • Helicobacter Infections/blood
  • Helicobacter pylori/physiology
  • Host-Pathogen Interactions
  • Iron, Dietary/blood
  • Male
  • Mice
  • Myelin Basic Protein/blood
  • Organ Specificity
  • Stomach/microbiology
  • Up-Regulation

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