Cyclooxygenase-2 is highly expressed in microglial-like cells in a murine model of prion disease.
Prion diseases, or transmissible spongiform encephalopathies, are a relatively rare group of chronic degenerative disorders afflicting both animals and humans, characterized by typical histopathological signs such as amyloid deposition, neuronal loss and spongiform changes. Despite the absence of a typical acute inflammatory response, the consistent microglial activation and astrocytosis, that are found in human pathologies as well as in animal models, suggests the existence of an ongoing inflammatory response in these neurodegenerative diseases. To investigate the role of cyclooxygenase-2 (COX-2) activity in the pathogenesis of chronic neurodegenerative diseases, we studied immunohistochemically the expression of this key enzyme in the formation of prostaglandins during inflammatory responses in a well characterized murine model of prion disease. We found that COX-2 is selectively up-regulated in glial cells presenting the typical morphology of activated microglia and that the number of COX-2-positive cells increases with the progression of the disease. The extensive microglial expression of COX-2, that is likely to be followed by a sustained enzymatic activity leading to the generation of prostaglandins as well as of oxygen free radicals, might have important effects on chronic neurodegeneration. Further functional experiments are required to elucidate the role of COX-2 activity in the pathogenesis of chronic neurodegenerative diseases.
Walsh
D T
DT
CNS Inflammation Group, Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
Perry
V H
VH
Minghetti
L
L
D000818:Animals; D051546:Cyclooxygenase 2; D018450:Disease Progression; D004790:Enzyme Induction; D005260:Female; D005609:Free Radicals; D005911:Gliosis / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000201:enzymology*; D009410:Nerve Degeneration; D017096:Prion Diseases / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species
D005609:Free Radicals; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases