Neurochemical Research

, Volume 33, Issue 11, pp 2318–2323 | Cite as

Chronic NMDA Administration Increases Neuroinflammatory Markers in Rat Frontal Cortex: Cross-Talk Between Excitotoxicity and Neuroinflammation

  • Yunyoung C. Chang
  • Hyung-Wook Kim
  • Stanley I. Rapoport
  • Jagadeesh S. Rao
Original Paper
First Online:
Received:
Accepted:

Abstract

Chronic N-Methyl-d-aspartate (NMDA) administration, a model of excitotoxicity, and chronic intracerebroventricular lipopolysaccharide infusion, a model of neuroinflammation, are reported to upregulate arachidonic acid incorporation and turnover in rat brain phospholipids as well as enzymes involved in arachidonic acid metabolism. This suggests cross-talk between signaling pathways of excitotoxicity and of neuroinflammation, involving arachidonic acid. To test whether chronic NMDA administrations to rats can upregulate brain markers of neuroinflammation, NMDA (25 mg/kg i.p.) or vehicle (1 ml saline/kg i.p.) was administered daily to adult male rats for 21 days. Protein and mRNA levels of cytokines and other inflammatory markers were measured in the frontal cortex using immunoblot and real-time PCR. Compared with chronic vehicle, chronic NMDA significantly increased protein and mRNA levels of interleukin-1beta, tumor necrosis factor alpha, glial fibrillary acidic protein and inducible nitric oxide synthase. Chronic NMDA receptor overactivation results in increased levels of neuroinflammatory markers in the rat frontal cortex, consistent with cross-talk between excitotoxicity and neuroinflammation. As both processes have been reported in a number of human brain diseases, NMDA receptor inhibitors might be of use in treating neuroinflammation in these diseases.

Keywords

Excitotoxicity Neuroinflammation Interleukin-1beta Tumor necrosis factor alpha Interleukin-10 Glial fibrillary acidic protein Inducible nitric oxide synthase Brain 

Abbreviations

NMDA

N-Methyl-d-aspartate

IL-1β

Interleukin-1beta

TNFα

Tumor necrosis factor alpha

GFAP

Glial fibrillary acid protein

iNOS

Inducible nitric oxide synthase

LPS

Lipopolysaccharide

NR

N-Methyl-d-aspartate receptor

AP-2

Activator protein-2

NF-κB

Nuclear factor-kappa B

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Notes

Acknowledgement

This work was entirely supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Yunyoung C. Chang
    • 1
  • Hyung-Wook Kim
    • 1
  • Stanley I. Rapoport
    • 1
  • Jagadeesh S. Rao
    • 1
  1. 1.Brain Physiology and Metabolism SectionNational Institute on Aging, National Institutes of HealthBethesdaUSA

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