Failure to sustain recovery of Na,K-ATPase function is a possible mechanism for striatal neurodegeneration in hypoxic-ischemic newborn piglets

W. Christopher Golden, Ansgar M. Brambrink, Richard J. Traystman, Lee J. Martin

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Hypoxia-ischemia (HI) in the newborn can lead to a variety of sensorimotor abnormalities, including movement and posture disorders. Striatal neurons undergo necrosis after HI in piglets, but mechanisms for this neuronal death are not understood. We tested the hypothesis that Na,K-ATPase is defective in striatum early after HI. Piglets (1 week old) were subjected to 30 min hypoxia (arterial oxygen saturation 30%) and then 7 min of airway occlusion (oxygen saturation 5%), producing asphyxic cardiac arrest. Animals were resuscitated and recovered for 3, 6, 12, and 24 h, respectively. Neuronal necrosis in the striatum is progressive [14]. Na,K-ATPase activity (percent of control) was 60, 98, 51, and 54% at 3, 6, 12, and 24 h after HI, respectively. Intrastriatal differences in enzyme activity were detected histochemically, with the putamen showing greater loss of Na,K-ATPase activity than caudate after 12 h recovery. Immunoblotting showed that the levels of the α3 isoform (localized exclusively to neurons) were 85, 115, 101, and 79% of sham control at 3, 6, 12, and 24 h, respectively. Levels of β1, the predominant β isoform, were similar to α3, while levels of the α1 subunit, the catalytic isoform found in neurons and glia, were 182, 179, 226, and 153% at the same recovery times. We conclude that early inactivation of Na,K-ATPase function participates in the pathogenesis of striatal neuron necrosis, but that loss of enzyme function early after HI is not caused by depletion of composite α/β subunits.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalMolecular Brain Research
Volume88
Issue number1-2
DOIs
StatePublished - Mar 31 2001

Keywords

  • Cerebral palsy
  • Excitotoxicity
  • Neuronal cell death
  • Nitric oxide
  • Oxidative stress
  • Peroxynitrite

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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