NR AYBP
AU Kim,J.I.; Jin,J.K.; Choi,E.K.; Spinner,D.; Rubenstein,R.; Carp,R.I.; Kim,Y.S.
TI Increased expression and localization of cyclooxygenase-2 in astrocytes of scrapie-infected mice
QU Journal of Neuroimmunology 2007 Jul; 187(1-2): 74-82
PT journal article; research support, non-u.s. gov't
AB A number of aspects of the pathogenesis of scrapie, the archetype disease of the transmissible spongiform encephalopathies (prion disorders), remain to be elucidated. There is increasing evidence that there are cerebral based inflammatory processes that may contribute to the pathogenesis and to the progression of a number of neurodegenerative disorders, including prion diseases. In peripheral tissues, a key element that controls the generation of proinflammatory mediators is the highly inducible protein cyclooxygenase-2 (COX-2). In this study, in order to examine the possible association of COX-2 with the pathogenesis of scrapie, we analyzed the expression level and the cellular localization of COX-2 in the brains of control and scrapie-infected mice. The COX-2 mRNA and protein levels were increased significantly compared to the control group of mice. By immunohistological analysis, intense immunoreactivity of COX-2 was localized primarily in reactive astrocytes, with virtually no staining in sections from control mice. The staining for COX-2 was co-localized with the pathological form of the prion protein (PrPsc) and with nuclear factor-kappa B (NF-kappaB). These results suggest that the upregulation of COX-2 expression in astrocytes may be related to the accumulation of PrPsc, and that COX-2 may then lead to the progression of scrapie, possibly by propagation of a cerebral inflammatory response.
MH Animals; Astrocytes/cytology/*metabolism/virology; Brain/*pathology/virology; Cyclooxygenase 2/*genetics/*metabolism; Dinoprostone/metabolism; Gene Expression Regulation, Enzymologic/*physiology; Male; Mice; Mice, Inbred C57BL; NF-kappa B/metabolism; Prions/metabolism; RNA, Messenger/biosynthesis; Reverse Transcriptase Polymerase Chain Reaction/methods; Scrapie/metabolism/*pathology
AD New York State Institute for Basic Research, Staten Island, New York, USA. jaeil.kim@case.edu
SP englisch
PO Niederlande