Chronic NMDA Administration Increases Neuroinflammatory Markers in Rat Frontal Cortex: Cross-Talk Between Excitotoxicity and Neuroinflammation |
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Authors: | Yunyoung C Chang Hyung-Wook Kim Stanley I Rapoport Jagadeesh S Rao |
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Institution: | (1) Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, 1S-126, Bethesda, MD 20892, USA |
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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. |
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Keywords: | Excitotoxicity Neuroinflammation Interleukin-1beta Tumor necrosis factor alpha Interleukin-10 Glial fibrillary acidic protein Inducible nitric oxide synthase Brain |
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