Altered expression and phosphorylation of N-methyl-D-aspartate receptors in piglet striatum after hypoxia - Ischemia

Anne Marie Guerguerian, Ansgar M. Brambrink, Richard J. Traystman, Richard L. Huganir, Lee J. Martin

Research output: Contribution to journalArticle

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Abstract

The mechanisms for the profound degeneration of striatal neurons after hypoxia - ischemia in newborns are not understood. We hypothesized that this striatal neurodegeneration is related to N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. Using a 1-week-old piglet model of hypoxia - ischemia, we evaluated whether the expression and phosphorylation of NMDA receptor subunits in striatum are modified with severity of evolving neuronal injury after hypoxia - ischemia. Protein levels of NR1, phosphorylated NR1 897serine, NR2A and NR2B in striatum were measured by immunoblotting after piglets underwent hypoxic - asphyxic cardiac arrest, cardiopulmonary resuscitation, and recovery for 3, 6, 12 or 24 h. In membrane fractions isolated from total striatum, mean NR1 and NR2A levels did not change significantly with time after hypoxia - ischemia compared to control; however, the levels of both NR1 and phosphorylated NR1 897serine correlated with neuronal injury in putamen, with higher levels associated with greater neuronal injury in individual animals. NR2B levels were increased at 24 h after hypoxia - ischemia. Astrocyte expression of NR2B was prominent after hypoxia - ischemia. We conclude that NMDA receptors are changed in striatum after neonatal hypoxia - ischemia and that abnormal NMDA receptor potentiation through increased NR1 phosphorylation may participate in the mechanisms of striatal neuron degeneration after hypoxia - ischemia.

Original languageEnglish (US)
Pages (from-to)66-80
Number of pages15
JournalMolecular Brain Research
Volume104
Issue number1-2
DOIs
StatePublished - Jul 15 2002

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Keywords

  • Excitotoxicity
  • Neuronal cell death

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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