The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor.

ABSTRACT: Prematurity is associated with perinatal neuroinflammation and injury. Screening for genetic modulators in an LPS murine model of preterm birth revealed the upregulation of Nr4a1, an orphan nuclear transcription factor that is normally absent or limited in embryonic brains. Concurrently, Nr4a1 was downregulated with magnesium sulfate (MgSO₄) and betamethasone (BMTZ) treatments administered to LPS exposed dams. To understand the role of Nr4a1 in perinatal brain injury, we compared the preterm neuroinflammatory response in Nr4a1 knockout (KO) versus wild type (wt) mice. Key inflammatory factors Il1b, Il6 and Tnf, and Iba1+ microglia were significantly lower in Nr4a1 KO versus wt brains exposed to LPS in utero. Treatment with MgSO₄/BMTZ mitigated the neuroinflammatory pr

SUBMITTER: Estrada SM 

PROVIDER: S-EPMC6944691 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature