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 K Georgieff, James G. Fox

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 (US)
Article numbere0142630
JournalPloS one
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2015

Bibliographical note

Funding Information:
Research reported in this publication was supported by Office of The Director of the National Institutes of Health under award number T3200010978, R01CA093405, P01CA028842-23, and National Institute of Environmental Health Sciences under award P30ES0022109. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Thanks to Bailey Clear, Lenzie Cheaney, and Christian Kaufman for assistance with animal manipulations, Laura Dahl for assistance with brain tissue qPCR processing, and Zeli Shen for H. pylori cultivation.

Fingerprint Dive into the research topics of 'Helicobacter pylori infection induces anemia, depletes serum iron storage, and alters local iron-related and adult brain gene expression in male INS-GAS mice'. Together they form a unique fingerprint.

Cite this