138081 20240826163725.0 10.1186/s40478-015-0198-y doi pmid:25853980 pmid pmc:PMC4369863 pmc altmetric:4029699 altmetric DZNE-2020-04403 English 610 Ulusoy, Ayse P:(DE-2719)2772760 0 First author dzne Neuron-to-neuron α-synuclein propagation in vivo is independent of neuronal injury. London 2015 Biomed Central online Crossref Springer Science and Business Media LLC 2015-03-24 print Crossref Springer Science and Business Media LLC 2015-12-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1724674958_22476 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Interneuronal propagation of α-synuclein has been demonstrated in a variety of experimental models and may be involved in disease progression during the course of human synucleinopathies. The aim of this study was to assess the role that neuronal injury or, vice versa, cell integrity could have in facilitating interneuronal α-synuclein transfer and consequent protein spreading in an in vivo animal model.Viral vectors carrying the DNA for human α-synuclein were injected into the rat vagus nerve to trigger protein overexpression in the medulla oblongata and consequent spreading of human α-synuclein toward pons, midbrain and forebrain. Two vector preparations sharing the same viral construct were manufactured using identical procedures with the exception of methods for their purification. They were also injected at concentrations that induced comparable levels of α-synuclein transduction/overexpression in the medulla oblongata. α-Synuclein load was associated with damage (at 6 weeks post injection) and death (at 12 weeks) of medullary neurons after treatment with only one of the two vector preparations. Of note, neuronal injury and degeneration was accompanied by a substantial reduction of caudo-rostral propagation of human α-synuclein.Interneuronal α-synuclein transfer, which underlies protein spreading from the medulla oblongata to more rostral brain regions in this rat model, is not a mere consequence of passive release from damaged or dead neurons. Neuronal injury and degeneration did not exacerbate α-synuclein propagation. In fact, data suggest that cell-to-cell passage of α-synuclein may be particularly efficient between intact, relatively healthy neurons. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 344 - Clinical and Health Care Research (POF3-344) G:(DE-HGF)POF3-344 POF3-344 POF III 1 2015-03-24 Crossref http://creativecommons.org/licenses/by/4.0 Dataset connected to CrossRef, PubMed, SNCA protein, human NLM Chemicals alpha-Synuclein NLM Chemicals Animals MeSH Brain: metabolism MeSH Disease Models, Animal MeSH Female MeSH Gene Transfer Techniques MeSH Humans MeSH Medulla Oblongata: metabolism MeSH Nerve Degeneration: metabolism MeSH Nerve Degeneration: pathology MeSH Neural Pathways: metabolism MeSH Neural Pathways: pathology MeSH Neurons: metabolism MeSH Neurons: pathology MeSH Parkinson Disease: metabolism MeSH Rats MeSH Rats, Sprague-Dawley MeSH alpha-Synuclein: metabolism MeSH Musgrove, Ruth E P:(DE-2719)2810507 1 dzne Rusconi, Raffaella P:(DE-2719)2810495 2 dzne Klinkenberg, Michael P:(DE-2719)2810845 3 dzne Helwig, Michael P:(DE-2719)2810665 4 dzne Schneider, Anja P:(DE-2719)2812035 5 dzne Di Monte, Donato A P:(DE-2719)2481741 6 Last author dzne 10.1186/s40478-015-0198-y : Springer Science and Business Media LLC, 2015-03-24 1 13 journal-article Crossref Acta Neuropathologica Communications 3 2015 2051-5960 10.1186/s40478-015-0198-y Vol. 3, no. 1, p. 13 PERI:(DE-600)2715589-4 1 3:1<13 13 Acta Neuropathologica Communications 3 2015 2051-5960 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369863 http://pub.dzne.de/record/138081/files/DZNE-2020-04403.pdf OpenAccess http://pub.dzne.de/record/138081/files/DZNE-2020-04403.pdf?subformat=pdfa pdfa OpenAccess oai:pub.dzne.de:138081 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2772760 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810507 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2810495 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810845 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2810665 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2812035 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2481741 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-344 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Clinical and Health Care Research 1 2015 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search JCR StatID:(DE-HGF)0100 StatID ACTA NEUROPATHOL COM : 2017 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal DBCoverage StatID:(DE-HGF)0500 StatID DOAJ WoS StatID:(DE-HGF)0111 StatID Science Citation Index Expanded DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC IF >= 5 StatID:(DE-HGF)9905 StatID ACTA NEUROPATHOL COM : 2017 DBCoverage StatID:(DE-HGF)0310 StatID NCBI Molecular Biology Database DBCoverage StatID:(DE-HGF)0300 StatID Medline DBCoverage StatID:(DE-HGF)0320 StatID PubMed Central DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List I:(DE-2719)1013008 AG Di Monte Neurodegeneration and Neuroprotection in Parkinson´s Disease 0 I:(DE-2719)1440011 AG Schneider Göttingen Translational Dementia Research Göttingen 1 journal VDB I:(DE-2719)1013008 I:(DE-2719)1440011 UNRESTRICTED FullTexts -- missing cx 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