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Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 22, Iss 5773, p 5773 (2021), Volume 22, Issue 11
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- 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.
- Subjects :
- TfR1
Placenta
T-Lymphocytes
medicine.disease_cause
Chorioamnionitis
neuroinflammation
Pregnancy
Homeostasis
Medicine
Biology (General)
Spectroscopy
chemistry.chemical_classification
neurodevelopment
Brain
General Medicine
Computer Science Applications
Chemistry
Premature Birth
Female
medicine.symptom
medicine.medical_specialty
QH301-705.5
Iron
HO-1
neural-immune
Inflammation
Peripheral blood mononuclear cell
Article
Catalysis
Inorganic Chemistry
Internal medicine
Receptors, Transferrin
Animals
RNA, Messenger
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Neuroinflammation
business.industry
Organic Chemistry
medicine.disease
Rats
Heme oxygenase
Oxidative Stress
Endocrinology
chemistry
Transferrin
Brain Injuries
peripheral immune activation
Heme Oxygenase (Decyclizing)
perinatal brain injury
business
Heme Oxygenase-1
Oxidative stress
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....7660d0fad7270da021921c1abced06f9