Isoflurane/nitrous oxide anesthesia induces increases in NMDA receptor subunit NR2B protein expression in the aged rat brain

Lana J. Mawhinney, Juan Pablo De Rivero Vaccari, Ofelia F. Alonso, Christopher A. Jimenez, Concepción Furones, W. Javier Moreno, Michael C. Lewis, W. Dalton Dietrich, Helen M. Bramlett

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Postoperative cognitive dysfunction, POCD, afflicts a large number of elderly surgical patients following surgery with general anesthesia. Mechanisms of POCD remain unclear. N-methyl-D-aspartate (NMDA) receptors, critical in learning and memory, that display protein expression changes with age are modulated by inhalation anesthetics. The aim of this study was to identify protein expression changes in NMDA receptor subunits and downstream signaling pathways in aged rats that demonstrated anesthesia-induced spatial learning impairments. Three-month-old and 18-month-old male Fischer 344 rats were randomly assigned to receive 1.8% isoflurane/70% nitrous oxide (N 2O) anesthesia for 4 h or no anesthesia. Spatial learning was assessed at 2 weeks and 3 months post-anesthesia in Morris water maze. Hippocampal and cortical protein lysates of 18-month-old rats were immunoblotted for activated caspase 3, NMDA receptor subunits, and extracellular-signal regulated kinase (ERK) 1/2. In a separate experiment, Ro 25-6981 (0.5 mg/kg dose) was administered by I.P. injection before anesthesia to 18-month-old rats. Immunoblotting of NR2B was performed on hippocampal protein lysates. At 3 months post-anesthesia, rats treated with anesthesia at 18-months-old demonstrated spatial learning impairment corresponding to acute and long-term increases in NR2B protein expression and a reduction in phospho-ERK1/2 in the hippocampus and cortex. Ro 25-6981 pretreatment attenuated the increase in acute NR2B protein expression. Our findings suggest a role for disruption of NMDA receptor mediated signaling pathways in the hippocampus and cortex of rats treated with isoflurane/ N 2O anesthesia at 18-months-old, leading to spatial learning deficits in these animals. A potential therapeutic intervention for anesthesia associated cognitive deficits is discussed.

Original languageEnglish (US)
Pages (from-to)23-34
Number of pages12
JournalBrain research
Volume1431
DOIs
StatePublished - Jan 11 2012

Keywords

  • Aging
  • Anesthesia
  • Extracellular signal regulated kinase (ERK)
  • Isoflurane
  • N-methyl-D-aspartate (NMDA) receptor subunit NR2B
  • Ro 25-6981

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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