title: Nurr1 expression is modified by inflammation in microglia.
abstract: Advances in neonatal care have allowed premature infants to survive at earlier gestational ages, but they are often afflicted with neurological delays or deficits. Maternal inflammation has been identified as a major risk factor for premature birth and once born, infants often require supplemental oxygen for survival. Nurr1 (NR4A2) is an orphan nuclear receptor with no known binding site and is essential for the growth of midbrain dopamine neurons. Others have reported that Nurr1 can act as an anti-inflammatory transcription factor in microglia and astrocytes and respond lipopolysaccharide (LPS). We have previously reported decreased numbers of oligodendrocytes and increased numbers of microglia in the mice exposed to both maternal inflammation and neonatal hyperoxia in the perinatal period. These studies tested the hypothesis that the combined exposures to inflammation and hyperoxia would increase Nurr1 expression in microglia in our mouse model and in an immortalized microglia cell line, BV2 cells. Our data indicate that Nurr1 protein expression is increased at postnatal day 0 and postnatal day 28 in whole-brain homogenates from mice exposed to LPS and hyperoxia. Alternatively, Nurr1 message is decreased at postnatal day 60 in isolated microglia, indicating that the increases in whole-brain homogenates may be due to other cell types. In BV2 cells, Nurr1 message in increased by exposure to hyperoxia, but this increase is attenuated in cells exposed to both LPS and hyperoxia. Although Nurr1 regulation is not straightforward, these data indicate that Nurr1 expression is increased in whole-brain homogenates in response to inflammation, but is decreased in isolated primary microglia and BV2 cells in response to similar inflammation. Our data support the hypothesis that Nurr1 expression may play a significant role in regulating inflammation in the brain and understanding the complex regulation of Nurr1 could lead to new therapeutic strategies.
authors.affiliation: aCenter for Perinatal Research, The Research Institute at Nationwide Children's Hospital bDepartment of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Lallier
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Graf
authors.forename: Gavisha R
authors.initials: GR
authors.lastname: Waidyarante
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Rogers
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D018496:Hyperoxia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000627:therapeutic use; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010100:Oxygen