title: Acute hypoxia modifies regulation of neuroglobin in the neonatal mouse brain.
abstract: Among endogenous adaptive systems to hypoxia, neuroglobin, a recently discovered heme protein, was suggested as a novel oxygen-dependent neuroprotectant. We aimed to characterize i) maturational age-related regulation of neuroglobin in the developing mouse brain under normoxic and hypoxic conditions, and ii) the role of hypoxia-inducible transcription factors (HIFs) as possible mediators of O(2)-dependent regulation of neuroglobin in vitro and in vivo. During early stages of postnatal brain maturation (P0-P14) neuroglobin mRNA levels significantly increased in developing mouse forebrains. By immunohistochemical analysis we confirmed expression of neuroglobin protein in the cytoplasm of developing neurons but not glial cells under normoxic conditions. Exposure of the immature brains (P0, P7) to acute (8% O(2), 6h) and chronic systemic hypoxia (10% O(2), 7 days) led to differential activation of neuroglobin varying with maturational stage (P0, P7) and severity of hypoxia. This observation may indicate that neuroglobin is involved in adaptive responses of immature neurons to acute hypoxia during an early stage of mouse brain maturation (P0). In response to activation of the HIF system by prolyl-4-hydroxylase inhibitor (FG-4497), neuroglobin mRNA expression was significantly up-regulated in primary mouse cortical neurons (DIV6) exposed to normoxia and hypoxia (1% O(2)) compared to non-treated controls. In conclusion, present results strongly indicate that cerebral regulation of neuroglobin is related to maturational stage and that hypoxia-induced neuroglobin up-regulation is modified by the HIF system.
authors.affiliation: Department of Pediatrics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hümmler
authors.forename: Christina
authors.initials: C
authors.lastname: Schneider
authors.forename: Andreas
authors.initials: A
authors.lastname: Giessl
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.forename: Gail
authors.initials: G
authors.lastname: Walkinshaw
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Regina
authors.initials: R
authors.lastname: Trollmann
mesh_terms: D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D061251:Primary Cell Culture; D013687:Telencephalon / Q000254:growth & development / Q000473:pathology*
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins