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Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.
- Source :
-
PloS one [PLoS One] 2015 Nov 17; Vol. 10 (11), pp. e0142630. Date of Electronic Publication: 2015 Nov 17 (Print Publication: 2015). - Publication Year :
- 2015
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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.
- Subjects :
- Anemia blood
Animals
Brain-Derived Neurotrophic Factor metabolism
Cell Size
Cytokines genetics
Cytokines metabolism
Erythrocytes physiology
Erythroid Cells metabolism
Erythropoietin blood
Ferritins blood
Gastric Mucosa metabolism
Gastritis blood
Gastritis microbiology
Gene Expression
Helicobacter Infections blood
Host-Pathogen Interactions
Male
Mice
Myelin Basic Protein blood
Organ Specificity
Stomach microbiology
Up-Regulation
Anemia microbiology
Brain metabolism
Helicobacter Infections complications
Helicobacter pylori physiology
Iron, Dietary blood
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26575645
- Full Text :
- https://doi.org/10.1371/journal.pone.0142630