Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation

Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation

Abstract The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we...

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Main Authors: Paula Ramos-Gonzalez, Susana Mato, Juan Carlos Chara, Alexei Verkhratsky, Carlos Matute, Fabio Cavaliere
Format: Article
Language:English
Published: Nature Publishing Group 2021-03-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-021-00175-w
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spelling doaj-6caf315b9ef544218a6118c4473e1b8b2021-04-04T11:45:16ZengNature Publishing Groupnpj Parkinson's Disease2373-80572021-03-017111110.1038/s41531-021-00175-wAstrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutationPaula Ramos-Gonzalez0Susana Mato1Juan Carlos Chara2Alexei Verkhratsky3Carlos Matute4Fabio Cavaliere5Department of Neurosciences, University of the Basque Country UPV/EHUDepartment of Neurosciences, University of the Basque Country UPV/EHUDepartment of Neurosciences, University of the Basque Country UPV/EHUAchucarro Basque Center for NeuroscienceDepartment of Neurosciences, University of the Basque Country UPV/EHUDepartment of Neurosciences, University of the Basque Country UPV/EHUAbstract The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we generated induced pluripotent stem cells (iPSC)-derived astrocytes from PD patients with LRRK2(G2019S) mutation and healthy donors of the similar age. In cell lines derived from PD patients, astrocytes were characterised by a significant decrease in S100B and GFAP-positive astrocytic profiles associated with marked decrease in astrocyte complexity. In addition, PD-derived astrocytes demonstrated aberrant mitochondrial morphology, decreased mitochondrial activity and ATP production along with an increase of glycolysis and increased production of reactive oxygen species. Taken together, our data indicate that astrocytic asthenia observed in patient-derived cultures with LRRK2(G2019S) mutation may contribute to neuronal death through decreased homoeostatic support, elevated oxidative stress and failed neuroprotection.https://doi.org/10.1038/s41531-021-00175-w
collection DOAJ
language English
format Article
sources DOAJ
author Paula Ramos-Gonzalez
Susana Mato
Juan Carlos Chara
Alexei Verkhratsky
Carlos Matute
Fabio Cavaliere
spellingShingle Paula Ramos-Gonzalez
Susana Mato
Juan Carlos Chara
Alexei Verkhratsky
Carlos Matute
Fabio Cavaliere
Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
npj Parkinson's Disease
author_facet Paula Ramos-Gonzalez
Susana Mato
Juan Carlos Chara
Alexei Verkhratsky
Carlos Matute
Fabio Cavaliere
author_sort Paula Ramos-Gonzalez
title Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_short Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_full Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_fullStr Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_full_unstemmed Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_sort astrocytic atrophy as a pathological feature of parkinson’s disease with lrrk2 mutation
publisher Nature Publishing Group
series npj Parkinson's Disease
issn 2373-8057
publishDate 2021-03-01
description Abstract The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we generated induced pluripotent stem cells (iPSC)-derived astrocytes from PD patients with LRRK2(G2019S) mutation and healthy donors of the similar age. In cell lines derived from PD patients, astrocytes were characterised by a significant decrease in S100B and GFAP-positive astrocytic profiles associated with marked decrease in astrocyte complexity. In addition, PD-derived astrocytes demonstrated aberrant mitochondrial morphology, decreased mitochondrial activity and ATP production along with an increase of glycolysis and increased production of reactive oxygen species. Taken together, our data indicate that astrocytic asthenia observed in patient-derived cultures with LRRK2(G2019S) mutation may contribute to neuronal death through decreased homoeostatic support, elevated oxidative stress and failed neuroprotection.
url https://doi.org/10.1038/s41531-021-00175-w
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