Home > Publications Database > Ischemic stroke causes Parkinson's disease-like pathology and symptoms in transgenic mice overexpressing alpha-synuclein. > print

001     163453
005     20230915090520.0
024 7 _ |a 10.1186/s40478-022-01327-6
|2 doi
024 7 _ |a pmid:35209932
|2 pmid
024 7 _ |a pmc:PMC8867857
|2 pmc
024 7 _ |a altmetric:123730747
|2 altmetric
037 _ _ |a DZNE-2022-00213
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Lohmann, Stephanie
|0 P:(DE-2719)2812190
|b 0
|e First author
|u dzne
245 _ _ |a Ischemic stroke causes Parkinson's disease-like pathology and symptoms in transgenic mice overexpressing alpha-synuclein.
260 _ _ |a London
|c 2022
|b Biomed Central
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1654865502_23357
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a The etiology of Parkinson's disease is poorly understood and is most commonly associated with advancing age, genetic predisposition, or environmental toxins. Epidemiological findings suggest that patients have a higher risk of developing Parkinson's disease after ischemic stroke, but this potential causality lacks mechanistic evidence. We investigated the long-term effects of ischemic stroke on pathogenesis in hemizygous TgM83 mice, which express human α-synuclein with the familial A53T mutation without developing any neuropathology or signs of neurologic disease for more than 600 days. We induced transient focal ischemia by middle cerebral artery occlusion in 2-month-old TgM83+/- mice and monitored their behavior and health status for up to 360 days post surgery. Groups of mice were sacrificed at 14, 30, 90, 180, and 360 days after surgery for neuropathological analysis of their brains. Motor deficits first appeared 6 months after focal ischemia and worsened until 12 months afterward. Immunohistochemical analysis revealed ischemia-induced neuronal loss in the infarct region and astrogliosis and microgliosis indicative of an inflammatory response, which was most pronounced at 14 days post surgery. Infarct volume and inflammation gradually decreased in size and severity until 180 days post surgery. Surprisingly, neuronal loss and inflammation were increased again by 360 days post surgery. These changes were accompanied by a continuous increase in α-synuclein aggregation, its neuronal deposition, and a late loss of dopaminergic neurons in the substantia nigra, which we detected at 360 days post surgery. Control animals that underwent sham surgery without middle cerebral artery occlusion showed no signs of disease or neuropathology. Our results establish a mechanistic link between ischemic stroke and Parkinson's disease and provide an animal model for studying possible interventions.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 0
536 _ _ |a 351 - Brain Function (POF4-351)
|0 G:(DE-HGF)POF4-351
|c POF4-351
|f POF IV
|x 1
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Alpha-synuclein
|2 Other
650 _ 7 |a Ischemia
|2 Other
650 _ 7 |a Ischemic stroke
|2 Other
650 _ 7 |a Parkinson’s disease
|2 Other
650 _ 7 |a Stroke
|2 Other
650 _ 7 |a Synucleinopathy
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Dopaminergic Neurons: pathology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Infarction, Middle Cerebral Artery: complications
|2 MeSH
650 _ 2 |a Inflammation: complications
|2 MeSH
650 _ 2 |a Ischemic Stroke
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Parkinson Disease: complications
|2 MeSH
650 _ 2 |a Parkinson Disease: genetics
|2 MeSH
650 _ 2 |a Parkinson Disease: pathology
|2 MeSH
650 _ 2 |a alpha-Synuclein: genetics
|2 MeSH
700 1 _ |a Grigoletto, Jessica
|0 P:(DE-2719)2812381
|b 1
|u dzne
700 1 _ |a Bernis, Maria Eugenia
|0 P:(DE-2719)2810557
|b 2
|u dzne
700 1 _ |a Pesch, Verena
|0 P:(DE-2719)2811818
|b 3
|u dzne
700 1 _ |a Ma, Liang
|b 4
700 1 _ |a Reithofer, Sara
|b 5
700 1 _ |a Tamgüney, Gültekin
|0 P:(DE-2719)2810376
|b 6
|u dzne
773 _ _ |a 10.1186/s40478-022-01327-6
|g Vol. 10, no. 1, p. 26
|0 PERI:(DE-600)2715589-4
|n 1
|p 26
|t Acta Neuropathologica Communications
|v 10
|y 2022
|x 2051-5960
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/163453/files/DZNE-2022-00213.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/163453/files/DZNE-2022-00213.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:163453
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)2812190
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 1
|6 P:(DE-2719)2812381
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 2
|6 P:(DE-2719)2810557
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 3
|6 P:(DE-2719)2811818
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 6
|6 P:(DE-2719)2810376
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-351
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Brain Function
|x 1
914 1 _ |y 2022
915 _ _ |a Creative Commons Attribution CC BY (No Version)
|0 LIC:(DE-HGF)CCBYNV
|2 V:(DE-HGF)
|b DOAJ
|d 2021-01-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2021-01-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2021-01-28
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2021-01-28
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2021-01-28
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2021-01-28
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b ACTA NEUROPATHOL COM : 2021
|d 2022-11-09
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2022-11-09
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2022-11-09
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2021-02-14T16:20:11Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2021-02-14T16:20:11Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Blind peer review
|d 2021-02-14T16:20:11Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2022-11-09
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2022-11-09
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2022-11-09
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2022-11-09
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2022-11-09
915 _ _ |a IF >= 5
|0 StatID:(DE-HGF)9905
|2 StatID
|b ACTA NEUROPATHOL COM : 2021
|d 2022-11-09
920 1 _ |0 I:(DE-2719)1013004
|k AG Vorberg
|l Prion Cell Biology
|x 0
920 1 _ |0 I:(DE-2719)1013022
|k AG Tamgüney 2
|l Prion and prion-like diseases
|x 1
920 1 _ |0 I:(DE-2719)1013033
|k AG Capasso
|l Immune Regulation
|x 2
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1013004
980 _ _ |a I:(DE-2719)1013022
980 _ _ |a I:(DE-2719)1013033
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21