Chorioamnionitis precipitates perinatal alterations of heme-oxygenase-1 (Ho-1) homeostasis in the developing rat brain

Maide Ozen, Yuma Kitase, Vikram Vasan, Christopher Burkhardt, Sindhu Ramachandra, Shenandoah Robinson, Lauren L. Jantzie

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number5773
JournalInternational journal of molecular sciences
Volume22
Issue number11
DOIs
StatePublished - Jun 1 2021

Keywords

  • HO-1
  • Neural-immune
  • Neurodevelopment
  • Neuroinflammation
  • Perinatal brain injury
  • Peripheral immune activation
  • TfR1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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