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NIA Intramural Research Program 2007 Summer Program |
"Barbara A. Hughes, Award of Excellence" -- July 30, 2007 Gerontology Research Center, Baltimore, Maryland Yunyoung Claire Chang, Summer IRTA University of Pennsylvania, Philadelphia Major: Biology, Sophomore Mentors: Stanley I. Rapoport, M.D., Jagadeesh Rao, Ph.D., Brain Physiology and Metabolism Section Poster Title: Chronic NMDA Administration Increases Neuroinflammatory Markers in Rat Frontal Cortex |
Abstract: Over-activation of NMDA receptor function is implicated in the pathophysiology of bipolar disorder. Chronic NMDA administration and LPS infusion are both known to up-regulate the expression of cytosolic phospholipase A2 (cPLA2) and activator protein 2 (AP-2) transcription factor subunits in the rat brain, while mood-stabilizers attenuate these effects. NMDA receptor antagonists have been shown to protect against LPS-induced neuroinflammation, suggesting a crosstalk between these two pathways. We further characterized if chronic administration of NMDA (25 mg/kg i.p.) to rats for 21 days would increase frontal cortex neuroinflammatory markers. We determined mRNA levels of interleukin -1b (IL-1b), tumor necrosis factor (TNFa), interleukin 10 (IL-10), glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) using the real-time PCR method. Chronic NMDA administration to rats significantly increased mRNA levels of IL-1b, TNFa, IL-10, GFAP and iNOS in the rat frontal cortex. The present study demonstrates that NMDA receptor over-activation is associated with increased neuroinflammatory markers in the rat frontal cortex. Developing drugs which attenuate over-activated NMDA receptor function may be beneficial in repressing neuroinflammation-mediated response. |
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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