{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:00:30Z","timestamp":1789642830312,"version":"4.0.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,9,3]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.93.18.9754","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"9754-9758","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":81,"title":["Heightened expression of tumor necrosis factor alpha, interleukin 1 alpha, and glial fibrillary acidic protein in experimental Creutzfeldt-Jakob disease in mice."],"prefix":"10.1073","volume":"93","author":[{"given":"R","family":"Kordek","sequence":"first","affiliation":[{"name":"Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V R","family":"Nerurkar","sequence":"additional","affiliation":[{"name":"Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P P","family":"Liberski","sequence":"additional","affiliation":[{"name":"Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Isaacson","sequence":"additional","affiliation":[{"name":"Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Yanagihara","sequence":"additional","affiliation":[{"name":"Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D C","family":"Gajdusek","sequence":"additional","affiliation":[{"name":"Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,9,3]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.18.9754","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:15:20Z","timestamp":1649859320000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.18.9754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,9,3]]},"references-count":0,"journal-issue":{"issue":"18","published-print":{"date-parts":[[1996,9,3]]}},"alternative-id":["10.1073\/pnas.93.18.9754"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.18.9754","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,9,3]]},"assertion":[{"value":"1996-09-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}