Differential vulnerability of immature murine neurons to oxygen-glucose deprivation

Xiangning Jiang, Dezhi Mu, Catherine Manabat, Anita A. Koshy, Stephan Christen, Martin G. Täuber, Zinaida S. Vexler, Donna M. Ferriero

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)224-232
Number of pages9
JournalExperimental Neurology
Volume190
Issue number1
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Keywords

  • Antioxidant defense
  • Brain development
  • Cortex
  • Differential susceptibility
  • Hippocampus
  • Ischemia
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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  • Cite this

    Jiang, X., Mu, D., Manabat, C., Koshy, A. A., Christen, S., Täuber, M. G., Vexler, Z. S., & Ferriero, D. M. (2004). Differential vulnerability of immature murine neurons to oxygen-glucose deprivation. Experimental Neurology, 190(1), 224-232. https://doi.org/10.1016/j.expneurol.2004.07.010