title: Effects of Lipopolysaccharide and Progesterone Exposures on Embryonic Cerebral Cortex Development in Mice.
abstract: Our objective was to determine if progesterone pretreatment could ameliorate the detrimental effects of lipopolysaccharide (LPS)-induced inflammation on cortical neurogenesis. Timed pregnant mouse dams (n = 8) were given intraperitoneal injections of progesterone (42 mg/kg) or vehicle on embryonic day 17.5. Two hours later, mice were given intraperitoneal LPS (140 μg/kg) or vehicle. Mice were sacrificed 16 hours later on embryonic day 18. Two-color immunofluorescence was performed with primary antibodies T-box transcription factor 2 (Tbr2), ionized calcium binding adapter molecule 1 (Iba1), cleaved caspase 3 (CC3), and 5-bromo-2'-deoxyuridine (BrdU). Cells were counted, and statistical analysis was determined using analysis of variance and Tukey-Kramer method. The Tbr2 intermediate neural progenitor cell density decreased after LPS exposure (P = .0022). Pre-exposure to progesterone statistically increased Tbr2 intermediate neural progenitors compared to LPS treatment alone and was similar to controls (P = .0022). After LPS exposure, microglia displayed an activated phenotype, and cell density was increased (P < .001). Cell death rates were low among study groups but was increased in LPS exposure groups compared to progesterone alone (P = .0015). Lipopolysaccharide-induced systemic inflammation reduces prenatal neurogenesis in mice. Pre-exposure with progesterone is associated with increased neurogenesis. Progesterone may protect the preterm brain from defects of neurogenesis induced by inflammation.
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, WA, USA ashlie.tronnes@gmail.com.
authors.forename: Ashlie A
authors.initials: AA
authors.lastname: Tronnes
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Koschnitzky
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Daza
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Hitti
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Jan Marino
authors.initials: JM
authors.lastname: Ramirez
authors.affiliation: Department of Neurological Surgery, Center for Integrative Brain Research, University of Washington School of Medicine, Seattle, WA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hevner
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology*; D004660:Encephalitis / Q000139:chemically induced / Q000196:embryology*; D005260:Female; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects*; D011374:Progesterone / Q000008:administration & dosage*
chemical_list: D008070:Lipopolysaccharides; D011374:Progesterone
keywords: inflammation; microglia; neurogenesis; prematurity; progesterone