Experimental Brain Research

, Volume 201, Issue 3, pp 479–488

Postnatal exposure to MK801 induces selective changes in GAD67 or parvalbumin

  • Christopher Paul Turner
  • Danielle DeBenedetto
  • Emily Ware
  • Robert Stowe
  • Andrew Lee
  • John Swanson
  • Caroline Walburg
  • Alexandra Lambert
  • Melissa Lyle
  • Priyanka Desai
  • Chun Liu
Research Article
  • 264 Downloads

Abstract

Brain injury during the last trimester to the first 1–4 years in humans is now thought to trigger an array of intellectual and emotional problems later in life, including disorders such as schizophrenia. In adult schizophrenic brains, there is a specific loss of neurons that co-express glutamic acid decarboxylase-parvalbumin (GAD67-PV). Loss of this phenotype is thought to occur in mature animals previously exposed to N-methyl-d-aspartate receptor (NMDAR) antagonists during late gestation or at postnatal day 7 (P7). However, in similarly treated animals, we have previously shown that GAD67 and PV are unaltered in the first 24 h. To more precisely define when changes in these markers first occur, we exposed rat pups (P7 or P6–P10) to the NMDAR antagonist MK801 and at P11 co-stained brain sections for GAD67 or PV. In the cingulate cortex, we found evidence for a reduction in PV (GAD67 levels were very low to undetectable). In contrast, in the somatosensory cortex, we found that expression of GAD67 was reduced, but PV remained stable. Further, repeated but not single doses of MK801 were necessary to see such changes. Thus, depending on the region, NMDAR antagonism appears to influence expression of PV or GAD67, but not both. These observations could not have been predicted by previous studies and raise important questions as to how the GAD67-PV phenotype is lost once animals reach maturity. More importantly, such differential effects may be of great clinical importance, given that cognitive deficits are seen in children exposed to anesthetics that act by blocking the NMDAR.

Keywords

Rat Neonatal Dizocilpine GABA Glutamate Calcium-binding protein 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Christopher Paul Turner
    • 1
  • Danielle DeBenedetto
    • 1
  • Emily Ware
    • 1
  • Robert Stowe
    • 1
  • Andrew Lee
    • 1
  • John Swanson
    • 1
  • Caroline Walburg
    • 1
  • Alexandra Lambert
    • 1
  • Melissa Lyle
    • 1
  • Priyanka Desai
    • 1
  • Chun Liu
    • 1
  1. 1.Neurobiology and AnatomyWake Forest University School of MedicineWinston-SalemUSA

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