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@ARTICLE{Lohmann:163453,
author = {Lohmann, Stephanie and Grigoletto, Jessica and Bernis,
Maria Eugenia and Pesch, Verena and Ma, Liang and Reithofer,
Sara and Tamgüney, Gültekin},
title = {{I}schemic stroke causes {P}arkinson's disease-like
pathology and symptoms in transgenic mice overexpressing
alpha-synuclein.},
journal = {Acta Neuropathologica Communications},
volume = {10},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DZNE-2022-00213},
pages = {26},
year = {2022},
abstract = {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.},
keywords = {Animals / Disease Models, Animal / Dopaminergic Neurons:
pathology / Humans / Infarction, Middle Cerebral Artery:
complications / Inflammation: complications / Ischemic
Stroke / Mice / Mice, Transgenic / Parkinson Disease:
complications / Parkinson Disease: genetics / Parkinson
Disease: pathology / alpha-Synuclein: genetics /
Alpha-synuclein (Other) / Ischemia (Other) / Ischemic stroke
(Other) / Parkinson’s disease (Other) / Stroke (Other) /
Synucleinopathy (Other)},
cin = {AG Vorberg / AG Tamgüney 2 / AG Capasso},
ddc = {610},
cid = {I:(DE-2719)1013004 / I:(DE-2719)1013022 /
I:(DE-2719)1013033},
pnm = {352 - Disease Mechanisms (POF4-352) / 351 - Brain Function
(POF4-351)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35209932},
pmc = {pmc:PMC8867857},
doi = {10.1186/s40478-022-01327-6},
url = {https://pub.dzne.de/record/163453},
}