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.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Hümmler N,Schneider C,Giessl A,Bauer R,Walkinshaw G,Gassmann M,Rascher W,Trollmann R

doi

10.1016/j.expneurol.2012.04.006

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

112-21

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(12)00158-6

journal_volume

236

pub_type

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