Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice
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 d...
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| Language: | en_US |
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Public Library of Science
2016
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| Online Access: | http://hdl.handle.net/1721.1/100697 https://orcid.org/0000-0002-3418-056X https://orcid.org/0000-0001-9307-6116 |
| _version_ | 1826215100214673408 |
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| author | Burns, Monika Muthupalani, Sureshkumar Ge, Zhongming Wang, Timothy C. Cunningham, Catriona Ennis, Kathleen Georgieff, Michael Fox, James G. Bakthavatchalu, Vasu |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Burns, Monika Muthupalani, Sureshkumar Ge, Zhongming Wang, Timothy C. Cunningham, Catriona Ennis, Kathleen Georgieff, Michael Fox, James G. Bakthavatchalu, Vasu |
| author_sort | Burns, Monika |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:16:33Z |
| format | Article |
| id | mit-1721.1/100697 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:16:33Z |
| publishDate | 2016 |
| publisher | Public Library of Science |
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| spelling | mit-1721.1/1006972022-09-29T19:20:17Z Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice Burns, Monika Muthupalani, Sureshkumar Ge, Zhongming Wang, Timothy C. Cunningham, Catriona Ennis, Kathleen Georgieff, Michael Fox, James G. Bakthavatchalu, Vasu Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Burns, Monika Muthupalani, Sureshkumar Ge, Zhongming Bakthavatchalu, Vasu Cunningham, Catriona Fox, James G. 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. National Institutes of Health (U.S.). Office of the Director (Award T3200010978) National Institutes of Health (U.S.). Office of the Director (Award R01CA093405) National Institutes of Health (U.S.). Office of the Director (Award P01CA028842-23) National Institute of Environmental Health Sciences (Award P30ES0022109) 2016-01-05T01:44:49Z 2016-01-05T01:44:49Z 2015-11 2015-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/100697 Burns, Monika, Sureshkumar Muthupalani, Zhongming Ge, Timothy C. Wang, Vasudevan Bakthavatchalu, Catriona Cunningham, Kathleen Ennis, Michael Georgieff, and James G. Fox. “Helicobacter Pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.” Edited by Ivo G. Boneca. PLoS ONE 10, no. 11 (November 17, 2015): e0142630. https://orcid.org/0000-0002-3418-056X https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1371/journal.pone.0142630 PLOS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Burns, Monika Muthupalani, Sureshkumar Ge, Zhongming Wang, Timothy C. Cunningham, Catriona Ennis, Kathleen Georgieff, Michael Fox, James G. Bakthavatchalu, Vasu Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice |
| title | Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice |
| title_full | Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice |
| title_fullStr | Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice |
| title_full_unstemmed | Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice |
| title_short | Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice |
| title_sort | helicobacter pylori infection induces anemia depletes serum iron storage and alters local iron related and adult brain gene expression in male ins gas mice |
| url | http://hdl.handle.net/1721.1/100697 https://orcid.org/0000-0002-3418-056X https://orcid.org/0000-0001-9307-6116 |
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