NR AGSA
AU Kordek,R.; Nerurkar,V.R.; Liberski,P.P.; Isaacson,S.; Yanagihara,R.; Gajdusek,D.C.
TI Heightened expression of tumor necrosis factor alpha, interleukin 1 alpha, and glial fibrillary acidic protein in experimental Creutzfeldt-Jakob disease in mice
QU Proceedings of the National Academy of Sciences of the United States of America 1996 Sep 3; 93(18): 9754-8
PT journal article
AB The ultrastructural pathology of myelinated axons in mice infected experimentally with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus is characterized by myelin sheath vacuolation that closely resembles that induced in murine spinal cord organotypic cultures by tumor necrosis factor alpha (TNF-alpha), a cytokine produced by astrocytes and macrophages. To clarify the role of TNF-alpha in experimental CJD, we investigated the expression of TNF-alpha in brain tissues from CJD virus-infected mice at weekly intervals after inoculation by reverse transcription-coupled PCR, Northern and Western blot analyses, and immunocytochemical staining. Neuropathological findings by electron microscopy, as well as expression of interleukin 1 alpha and glial fibrillary acidic protein, were concurrently monitored. As determined by reverse transcription-coupled PCR, the expression of TNF-alpha, interleukin 1 alpha, and glial fibrillary acidic protein was increased by approximately 200-fold in the brains of CJD virus-inoculated mice during the course of disease. By contrast, beta-actin expression remained unchanged. Progressively increased expression of TNF-alpha in CJD virus-infected brain tissues was verified by Northern and Western blot analyses, and astrocytes in areas with striking myelin sheath vacuolation were intensely stained with an antibody against murine TNF-alpha. The collective findings of TNF-alpha overexpression during the course of clinical disease suggest that TNF-alpha may mediate the myelin sheath vacuolation observed in experimental CJD.
IN Bei Mäusen soll eine CJD-Infektion eine 200-fache Steigerung der Expression von TNF-alpha, Interleukin 1 alpha und dem sauren fibrillären Gliaprotein bewirken, während keine Veränderung der Expression von Beta-Aktin beobachtet wurde.
ZR 50
MH Animal; Base Sequence; Blotting, Northern; Blotting, Western; Brain/metabolism; Creutzfeldt-Jakob Syndrome/*metabolism; Glial Fibrillary Acidic Protein/*biosynthesis; Human; Interleukin-1/*biosynthesis; Male; Mice; Middle Age; Molecular Sequence Data; Myelin Sheath/ultrastructure; Polymerase Chain Reaction; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Necrosis Factor/*biosynthesis; Up-Regulation
AD Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892, USA
SP englisch
PO USA