Differential vulnerability of immature murine neurons to oxygen-glucose deprivation

Jiang, X; Mu, D; Manabat, C; Koshy, AA; Christen, S; Täuber, MG; Vexler, ZS; Ferriero, DM (2004). Differential vulnerability of immature murine neurons to oxygen-glucose deprivation. Experimental neurology, 190(1), pp. 224-32. San Diego, Calif.: Elsevier 10.1016/j.expneurol.2004.07.010

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In vivo studies support selective neuronal vulnerability to hypoxia-ischemia (HI) in the developing brain. Since differences in intrinsic properties of neurons might be responsible, pure cultures containing immature neurons (6-8 days in vitro) isolated from mouse cortex and hippocampus, regions chosen for their marked vulnerability to oxidative stress, were studied under in vitro ischemic conditions-oxygen-glucose deprivation (OGD). Twenty-four hours of reoxygenation after 2.5 h of OGD induced significantly greater cell death in hippocampal than in cortical neurons (67.8% vs. 33.4%, P = 0.0068). The expression of neuronal nitric oxide synthase (nNOS) protein, production of nitric oxide (NO), and reactive oxygen species (ROS), as well as glutathione peroxidase (GPx) activity and intracellular levels of reduced glutathione (GSH), were measured as indicators of oxidative stress. Hippocampal neurons had markedly higher nNOS expression than cortical neurons by 24 h of reoxygenation, which coincided with an increase in NO production, and significantly greater ROS accumulation. GPx activity declined significantly in hippocampal but not in cortical neurons at 4 and 24 h after OGD. The decrease in GSH level in hippocampal neurons correlated with the decline of GPx activity. Our data suggest that developing hippocampal neurons are more sensitive to OGD than cortical neurons. This finding supports our in vivo studies showing that mouse hippocampus is more vulnerable than cortex after neonatal HI. An imbalance between excess prooxidant production (increased nNOS expression, and NO and ROS production) and insufficient antioxidant defenses created by reduced GPx activity and GSH levels may, in part, explain the higher susceptibility to OGD of immature hippocampal neurons.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Christen, Stephan, Täuber, Martin G.

ISSN:

0014-4886

ISBN:

15473995

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:55

Last Modified:

05 Dec 2022 14:17

Publisher DOI:

10.1016/j.expneurol.2004.07.010

PubMed ID:

15473995

Web of Science ID:

000224822100020

URI:

https://boris.unibe.ch/id/eprint/23681 (FactScience: 43466)

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