Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation

Abstract The pathological hallmark of Parkinson’s disease (PD) is the formation of Lewy bodies containing aggregated alpha-synuclein (α-syn). Although PD is associated with these distinct histological changes, other pathological features such as microvascular alterations have been linked to neurodeg...

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Autores principales:	Osama Elabi, Abderahim Gaceb, Robert Carlsson, Thomas Padel, Rana Soylu-Kucharz, Irene Cortijo, Wen Li, Jia-Yi Li, Gesine Paul
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ec7f83bec5c641f586d67ee9ecc25ce2
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spelling	oai:doaj.org-article:ec7f83bec5c641f586d67ee9ecc25ce22021-12-02T14:01:36ZHuman α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation10.1038/s41598-020-80889-82045-2322https://doaj.org/article/ec7f83bec5c641f586d67ee9ecc25ce22021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80889-8https://doaj.org/toc/2045-2322Abstract The pathological hallmark of Parkinson’s disease (PD) is the formation of Lewy bodies containing aggregated alpha-synuclein (α-syn). Although PD is associated with these distinct histological changes, other pathological features such as microvascular alterations have been linked to neurodegeneration. These changes need to be investigated as they create a hostile brain microenvironment and may contribute to the development and progression of the disease. We use a human α-syn overexpression mouse model that recapitulates some of the pathological features of PD in terms of progressive aggregation of human α-syn, impaired striatal dopamine fiber density, and an age-dependent motor deficit consistent with an impaired dopamine release. We demonstrate for the first time in this model a compromised blood–brain barrier integrity and dynamic changes in vessel morphology from angiogenesis at earlier stages to vascular regression at later stages. The vascular alterations are accompanied by a pathological activation of pericytes already at an early stage without changing overall pericyte density. Our data support and further extend the occurrence of vascular pathology as an important pathophysiological aspect in PD. The model used provides a powerful tool to investigate disease-modifying factors in PD in a temporal sequence that might guide the development of new treatments.Osama ElabiAbderahim GacebRobert CarlssonThomas PadelRana Soylu-KucharzIrene CortijoWen LiJia-Yi LiGesine PaulNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Osama Elabi Abderahim Gaceb Robert Carlsson Thomas Padel Rana Soylu-Kucharz Irene Cortijo Wen Li Jia-Yi Li Gesine Paul Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation
description	Abstract The pathological hallmark of Parkinson’s disease (PD) is the formation of Lewy bodies containing aggregated alpha-synuclein (α-syn). Although PD is associated with these distinct histological changes, other pathological features such as microvascular alterations have been linked to neurodegeneration. These changes need to be investigated as they create a hostile brain microenvironment and may contribute to the development and progression of the disease. We use a human α-syn overexpression mouse model that recapitulates some of the pathological features of PD in terms of progressive aggregation of human α-syn, impaired striatal dopamine fiber density, and an age-dependent motor deficit consistent with an impaired dopamine release. We demonstrate for the first time in this model a compromised blood–brain barrier integrity and dynamic changes in vessel morphology from angiogenesis at earlier stages to vascular regression at later stages. The vascular alterations are accompanied by a pathological activation of pericytes already at an early stage without changing overall pericyte density. Our data support and further extend the occurrence of vascular pathology as an important pathophysiological aspect in PD. The model used provides a powerful tool to investigate disease-modifying factors in PD in a temporal sequence that might guide the development of new treatments.
format	article
author	Osama Elabi Abderahim Gaceb Robert Carlsson Thomas Padel Rana Soylu-Kucharz Irene Cortijo Wen Li Jia-Yi Li Gesine Paul
author_facet	Osama Elabi Abderahim Gaceb Robert Carlsson Thomas Padel Rana Soylu-Kucharz Irene Cortijo Wen Li Jia-Yi Li Gesine Paul
author_sort	Osama Elabi
title	Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation
title_short	Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation
title_full	Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation
title_fullStr	Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation
title_full_unstemmed	Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation
title_sort	human α-synuclein overexpression in a mouse model of parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ec7f83bec5c641f586d67ee9ecc25ce2
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Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation

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