We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cyclooxygenase-1 mediates prostaglandin E<sub>2</sub> elevation and contextual memory impairment in a model of sustained hippocampal interleukin-1β expression.
- Authors
Matousek, Sarah B.; Hein, Amy M.; Shaftel, Solomon S.; Olschowka, John A.; Kyrkanides, Stephanos; O'Banion, M. Kerry
- Abstract
J. Neurochem. (2010) 114, 247–258. Interleukin (IL)-1β is a proinflammatory cytokine implicated in several neurodegenerative disorders. Downstream actions of IL-1β include production of prostaglandin (PG) E2 by increasing expression of cyclooxygenase (COX) enzymes and prostaglandin E synthase (PGES) isoforms. We recently developed a transgenic mouse carrying a dormant human IL-1β eXcisional Activation Transgene (XAT) for conditional and chronic up-regulation of IL-1β in selected brain regions. This model is characterized by regionally specific glial activation, immune cell recruitment, and induction of cytokines and chemokines. Here, we aimed to elucidate the effects of long-term IL-1β expression on the PGE2 synthetic pathway and to determine the effects of PGs on inflammation and memory in our model. As expected, PGE2 levels were significantly elevated after IL-1β up-regulation. Quantitative real-time PCR analysis indicated significant induction of mRNAs for COX-1 and membranous PGES-1, but not COX-2 or other PGES isoforms. Immunohistochemistry revealed elevation of COX-1 but no change in COX-2 following sustained IL-1β production. Furthermore, pharmacological inhibition of COX-1 and use of COX-1 knockout mice abrogated IL-1β-mediated PGE2 increases. Although COX-1 deficient mice did not present a dramatically altered neuroinflammatory phenotype, they did exhibit improved contextual fear memory. This data suggests a unique role for COX-1 in mediating chronic neuroinflammatory effects through PGE2 production.
- Publication
Journal of Neurochemistry, 2010, Vol 114, Issue 1, p247
- ISSN
0022-3042
- Publication type
Academic Journal
- DOI
10.1111/j.1471-4159.2010.06759.x