{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:27:51Z","timestamp":1790422071648,"version":"4.1.0"},"reference-count":70,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,1,15]],"date-time":"2017-01-15T00:00:00Z","timestamp":1484438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS089622"],"award-info":[{"award-number":["NS089622"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Misfolded \u03b1-synuclein (\u03b1S) is hypothesized to spread throughout the central nervous system (CNS) by neuronal connectivity leading to widespread pathology. Increasing evidence indicates that it also has the potential to invade the CNS via peripheral nerves in a prion-like manner. On the basis of the effectiveness following peripheral routes of prion administration, we extend our previous studies of CNS neuroinvasion in M83 \u03b1S transgenic mice following hind limb muscle (intramuscular [i.m.]) injection of \u03b1S fibrils by comparing various peripheral sites of inoculations with different \u03b1S protein preparations. Following intravenous injection in the tail veins of homozygous M83 transgenic (M83\n            <jats:sup>+\/+<\/jats:sup>\n            ) mice, robust \u03b1S pathology was observed in the CNS without the development of motor impairments within the time frame examined. Intraperitoneal (i.p.) injections of \u03b1S fibrils in hemizygous M83 transgenic (M83\n            <jats:sup>+\/\u2212<\/jats:sup>\n            ) mice resulted in CNS \u03b1S pathology associated with paralysis. Interestingly, injection with soluble, nonaggregated \u03b1S resulted in paralysis and pathology in only a subset of mice, whereas soluble \u039471-82 \u03b1S, human \u03b2S, and keyhole limpet hemocyanin (KLH) control proteins induced no symptoms or pathology. Intraperitoneal injection of \u03b1S fibrils also induced CNS \u03b1S pathology in another \u03b1S transgenic mouse line (M20), albeit less robustly in these mice. In comparison, i.m. injection of \u03b1S fibrils was more efficient in inducing CNS \u03b1S pathology in M83 mice than i.p. or tail vein injections. Furthermore, i.m. injection of soluble, nonaggregated \u03b1S in M83\n            <jats:sup>+\/\u2212<\/jats:sup>\n            mice also induced paralysis and CNS \u03b1S pathology, although less efficiently. These results further demonstrate the prion-like characteristics of \u03b1S and reveal its efficiency to invade the CNS via multiple routes of peripheral administration.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The misfolding and accumulation of \u03b1-synuclein (\u03b1S) inclusions are found in a number of neurodegenerative disorders and is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Similar characteristics have been observed between the infectious prion protein and \u03b1S, including its ability to spread from the peripheral nervous system and along neuroanatomical tracts within the central nervous system. In this study, we extend our previous results and investigate the efficiency of intravenous (i.v.), intraperitoneal (i.p.), and intramuscular (i.m.) routes of injection of \u03b1S fibrils and other protein controls. Our data reveal that injection of \u03b1S fibrils via these peripheral routes in \u03b1S-overexpressing mice are capable of inducing a robust \u03b1S pathology and in some cases cause paralysis. Furthermore, soluble, nonaggregated \u03b1S also induced \u03b1S pathology, albeit with much less efficiency. These findings further support and extend the idea of \u03b1S neuroinvasion from peripheral exposures.\n          <\/jats:p>","DOI":"10.1128\/jvi.02095-16","type":"journal-article","created":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T04:00:46Z","timestamp":1479355246000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":93,"title":["Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of \u03b1-Synuclein Fibrils"],"prefix":"10.1128","volume":"91","author":[{"given":"Jacob I.","family":"Ayers","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, Florida, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA"},{"name":"McKnight Brain Institute, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieu M.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, Florida, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, Florida, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasie K.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, Florida, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary A.","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, Florida, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara J.","family":"Riffe","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, Florida, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit I.","family":"Giasson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, Florida, USA"},{"name":"Center for Translational Research in 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