NR AMOW
AU Williams,A.; van Dam,A.M.; Ritchie,D.; Eikelenboom,P.; Fraser,H.
TI Immunocytochemical appearance of cytokines, prostaglandin E2 and lipocortin-1 in the CNS during the incubation period of murine scrapie correlates with progressive PrP accumulations
QU Brain Research 1997 Apr 18; 754(1-2): 171-80
PT journal article
AB The appearance of immunoreactive interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha, prostaglandin (PG) E2 and lipocortin-1 in the central nervous system was investigated during the development of lesions in a 301V/VM murine scrapie model. Focal PrPsc deposition was present after 30 days of the 115-120 day incubation period; this immunoreactivity increased in intensity and distribution thereafter. Staining for IL-1ß and TNF alpha in perivascular macrophages, and PGE2 immunoreactivity in astrocytes, was detected in those areas showing PrPsc deposition from 60 days. Increased GFAP and F4/80 immunoreactivity, indicating activation of astrocytes and microglia, was also evident in these areas from 60 days. Glial cytokine and lipocortin immunoreactivity was detected after 90 days, in the absence of clinical signs. The disease-induced cytokine, PG and lipocortin immunoreactivity occurred only in those brain areas showing PrPsc deposition, glial activation and, in later stages, vacuolation. These findings support the concept that PrPsc deposition induces glial cytokine production. These glial cytokines may contribute to the development of the pathological lesions in scrapie.
MH Animal; Annexin I/*biosynthesis; Brain/immunology/*metabolism/pathology; Cytokines/*biosynthesis; Dinoprostone/*metabolism; Glial Fibrillary Acidic Protein/analysis; Hippocampus/immunology/metabolism/pathology; Immunohistochemistry; Interleukin-1/biosynthesis; Interleukin-6/biosynthesis; Macrophages/immunology/metabolism/pathology; Mice; Mice, Inbred Strains; Prions/biosynthesis; Scrapie/immunology/metabolism/*physiopathology; Support, Non-U.S. Gov't; Thalamus/immunology/metabolism/pathology; Time Factors; Tumor Necrosis Factor/biosynthesis
AD Alun Williams, Diane Ritchie, Hugh Fraser, Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh, EH9 3JF, UK; Anne-Marie Van Dam, Research Institute Neurosciences Free University, Faculty of Medicine, Department of Pharmacology, Van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands; Pieter Eikelenboom, Research Institute Neurosciences Free University, Faculty of Medicine, Department of Psychiatry, Valeriuskliniek, Valeriusplein 9, 1075 BG Amsterdam, Netherlands
SP englisch
PO Niederlande