Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain
Chorioamnionitis (CHORIO), placental insufficiency, and preterm birth are well-known antecedents of perinatal brain injury (PBI). Heme-oxygenase-1 (HO-1) is an important inducible enzyme in oxidative and inflammatory conditions. In the brain, HO-1 and the iron regulatory receptor, transferrin recept...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/11/5773 |
| _version_ | 1797532265459220480 |
|---|---|
| author | Maide Ozen Yuma Kitase Vikram Vasan Christopher Burkhardt Sindhu Ramachandra Shenandoah Robinson Lauren L. Jantzie |
| author_facet | Maide Ozen Yuma Kitase Vikram Vasan Christopher Burkhardt Sindhu Ramachandra Shenandoah Robinson Lauren L. Jantzie |
| author_sort | Maide Ozen |
| collection | DOAJ |
| description | Chorioamnionitis (CHORIO), placental insufficiency, and preterm birth are well-known antecedents of perinatal brain injury (PBI). Heme-oxygenase-1 (HO-1) is an important inducible enzyme in oxidative and inflammatory conditions. In the brain, HO-1 and the iron regulatory receptor, transferrin receptor-1 (TfR1), are known to be involved in iron homeostasis, oxidative stress, and cellular adaptive mechanisms. However, the role of HO pathway in the pathophysiology of PBI has not been previously studied. In this study, we set out to define the ontogeny of the HO pathway in the brain and determine if CHORIO changed its normal developmental regulation. We also aimed to determine the role of HO-1/TfR1 in CHORIO-induced neuroinflammation and peripheral inflammation in a clinically relevant rat model of PBI. We show that HO-1, HO-2, and TfR1 expression are developmentally regulated in the brain during the perinatal period. CHORIO elevates HO-1 and TfR1 mRNA expression in utero and in the early postnatal period and results in sustained increase in HO-1/TfR1 ratios in the brain. This is associated with neuroinflammatory and peripheral immune phenotype supported by a significant increase in brain mononuclear cells and peripheral blood double negative T cells suggesting a role of HO-1/TfR1 pathway dysregulation in CHORIO-induced neuroinflammation. |
| first_indexed | 2024-03-10T10:57:35Z |
| format | Article |
| id | doaj.art-7b7c21c5588f4632bb9a665490f3fad8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:57:35Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7b7c21c5588f4632bb9a665490f3fad82023-11-21T21:47:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211577310.3390/ijms22115773Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat BrainMaide Ozen0Yuma Kitase1Vikram Vasan2Christopher Burkhardt3Sindhu Ramachandra4Shenandoah Robinson5Lauren L. Jantzie6Department of Pediatrics, Neonatal-Perinatal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pediatrics, Neonatal-Perinatal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pediatrics, Neonatal-Perinatal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pediatrics, Neonatal-Perinatal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pediatrics, Neonatal-Perinatal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pediatrics, Neonatal-Perinatal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pediatrics, Neonatal-Perinatal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAChorioamnionitis (CHORIO), placental insufficiency, and preterm birth are well-known antecedents of perinatal brain injury (PBI). Heme-oxygenase-1 (HO-1) is an important inducible enzyme in oxidative and inflammatory conditions. In the brain, HO-1 and the iron regulatory receptor, transferrin receptor-1 (TfR1), are known to be involved in iron homeostasis, oxidative stress, and cellular adaptive mechanisms. However, the role of HO pathway in the pathophysiology of PBI has not been previously studied. In this study, we set out to define the ontogeny of the HO pathway in the brain and determine if CHORIO changed its normal developmental regulation. We also aimed to determine the role of HO-1/TfR1 in CHORIO-induced neuroinflammation and peripheral inflammation in a clinically relevant rat model of PBI. We show that HO-1, HO-2, and TfR1 expression are developmentally regulated in the brain during the perinatal period. CHORIO elevates HO-1 and TfR1 mRNA expression in utero and in the early postnatal period and results in sustained increase in HO-1/TfR1 ratios in the brain. This is associated with neuroinflammatory and peripheral immune phenotype supported by a significant increase in brain mononuclear cells and peripheral blood double negative T cells suggesting a role of HO-1/TfR1 pathway dysregulation in CHORIO-induced neuroinflammation.https://www.mdpi.com/1422-0067/22/11/5773HO-1TfR1neuroinflammationperipheral immune activationperinatal brain injuryneurodevelopment |
| spellingShingle | Maide Ozen Yuma Kitase Vikram Vasan Christopher Burkhardt Sindhu Ramachandra Shenandoah Robinson Lauren L. Jantzie Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain International Journal of Molecular Sciences HO-1 TfR1 neuroinflammation peripheral immune activation perinatal brain injury neurodevelopment |
| title | Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain |
| title_full | Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain |
| title_fullStr | Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain |
| title_full_unstemmed | Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain |
| title_short | Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain |
| title_sort | chorioamnionitis precipitates perinatal alterations of heme oxygenase 1 ho 1 homeostasis in the developing rat brain |
| topic | HO-1 TfR1 neuroinflammation peripheral immune activation perinatal brain injury neurodevelopment |
| url | https://www.mdpi.com/1422-0067/22/11/5773 |
| work_keys_str_mv | AT maideozen chorioamnionitisprecipitatesperinatalalterationsofhemeoxygenase1ho1homeostasisinthedevelopingratbrain AT yumakitase chorioamnionitisprecipitatesperinatalalterationsofhemeoxygenase1ho1homeostasisinthedevelopingratbrain AT vikramvasan chorioamnionitisprecipitatesperinatalalterationsofhemeoxygenase1ho1homeostasisinthedevelopingratbrain AT christopherburkhardt chorioamnionitisprecipitatesperinatalalterationsofhemeoxygenase1ho1homeostasisinthedevelopingratbrain AT sindhuramachandra chorioamnionitisprecipitatesperinatalalterationsofhemeoxygenase1ho1homeostasisinthedevelopingratbrain AT shenandoahrobinson chorioamnionitisprecipitatesperinatalalterationsofhemeoxygenase1ho1homeostasisinthedevelopingratbrain AT laurenljantzie chorioamnionitisprecipitatesperinatalalterationsofhemeoxygenase1ho1homeostasisinthedevelopingratbrain |