{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:10:38Z","timestamp":1791349838513,"version":"4.3.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,4,27]],"date-time":"2004-04-27T00:00:00Z","timestamp":1083024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the transmissible spongiform encephalopathies (TSE), accumulation of the abnormal disease\u2010specific prion protein is associated with neurodegeneration. Previous data suggested that abnormal prion protein (PrP) could induce neuronal pathology only when neurons expressed the normal form of PrP, but conflicting evidence also has been reported. Understanding whether neuronal PrP expression is required for TSE neuropathological damage in vivo is essential for determining the mechanism of TSE pathogenesis. Therefore, these experiments were designed to study scrapie pathogenesis in vivo in the absence of neuronal PrP expression. Hamster scrapie (strain 263K) was used to infect transgenic mice expressing hamster PrP in the brain only in astrocytes. These mice previously were shown to develop clinical scrapie, but it was unclear whether the brain pathology was caused by damage to astrocytes, neurons, or other cell types. In this electron microscopic study, neurons demonstrated TSE\u2010specific pathology despite lacking PrP expression. Abnormal PrP was identified around astrocytes, primarily in the extracellular spaces of the neuropil, but astrocytes showed only reactive changes and no damage. Therefore, in this model the pathogenesis of the disease appeared to involve neuronal damage associated with extracellular astrocytic accumulation of abnormal PrP acting upon nearby PrP\u2010negative neurons or triggering the release of non\u2010PrP neurotoxic factors from astrocytes.<\/jats:p>","DOI":"10.1002\/ana.20093","type":"journal-article","created":{"date-parts":[[2004,4,27]],"date-time":"2004-04-27T20:01:02Z","timestamp":1083096062000},"page":"781-792","source":"Crossref","is-referenced-by-count":91,"title":["Scrapie\u2010specific neuronal lesions are independent of neuronal PrP expression"],"prefix":"10.1002","volume":"55","author":[{"given":"Martin","family":"Jeffrey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Goodsir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Race","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Chesebro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,4,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a072647"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.55782\/ane-2002-1436","article-title":"Neuropathology of variant Creutzfeldt\u2010Jakob disease","volume":"62","author":"Ironside JW","year":"2002","journal-title":"Acta Neurobiol Exp"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.20506\/rst.21.2.1340"},{"key":"e_1_2_6_5_2","first-page":"67","volume-title":"Prion biology and diseases","author":"Prusiner SB","year":"1999"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90360-3"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90298-X"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.2.375"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1053\/jcpa.2001.0516"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01470.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1523\/JNEUROSCI.23-02-00462.2003","article-title":"In vivo and in vitro neurotoxicity of the human prion protein (PrP) fragment P118\u2013135 independently of PrP expression","volume":"23","author":"Chabry J","year":"2003","journal-title":"J Neurosci"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/379339a0"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0731105.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0316"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073619"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073725"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.20.6057"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.18800-0"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(89)90023-2"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1997.tb01191.x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.21.10106-10112.2001"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.7.1213"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90105-1"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91477-X"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90113-9"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1994.tb01007.x"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/neur.1996.0014"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00692148"},{"key":"e_1_2_6_29_2","first-page":"373","volume-title":"Tubulovesicular structures. Light and electron microscopic neuropathology of slow virus disorders","author":"Liberski PP","year":"1993"},{"key":"e_1_2_6_30_2","first-page":"665","article-title":"Spiroplasma\u2010like inclusions in Creutzfeldt\u2010Jakob disease","volume":"103","author":"Bastian FO","year":"1979","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1986.tb00047.x"},{"key":"e_1_2_6_32_2","first-page":"349","volume-title":"Light and electron microscopic neuropathology of slow virus disorders","author":"Liberski PP","year":"1993"},{"key":"e_1_2_6_33_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00401-003-0690-5","article-title":"Sub\u2010cellular pathology of scrapie: coated pits are increased in PrP codon 136 alanine homozygous scrapie\u2010affected sheep","volume":"106","author":"Ersdal C","year":"2003","journal-title":"Acta Neuropathol"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(02)00045-X"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000579200"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(01)57022-9"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090187"},{"key":"e_1_2_6_38_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.55782\/ane-2002-1430","article-title":"Ultrastructural studies of experimental scrapie and Creutzfeldt\u2010Jakob disease in hamsters. I. Alterations of myelinated axons","volume":"62","author":"Liberski PP","year":"2002","journal-title":"Acta Neurobiol Exp"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1997.0133"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi026872q"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306177200"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.20093","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.20093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:37:20Z","timestamp":1734327440000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.20093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4,27]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1002\/ana.20093"],"URL":"https:\/\/doi.org\/10.1002\/ana.20093","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4,27]]}}}