Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease

Inflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated that the basal inflammatory tone differed between brain regions and, consequently, the reaction generated to a pro-inflammatory stimulus was different. In this study, we asse...

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Autores: Basurco, Leyre, Abellanas, Miguel Ángel, Ayerra, Leyre, Conde, Enrique, Vinueza-Gavilanes, Rodrigo, Luquin, Esther, Vales, Africa, Vilas, Amaia, San Martin-Uriz, Patxi, Tamayo Uria, Ibon, Alonso Roldán, Marta, Hernaez, Mikel, González-Aseguinolaza, Gloria, Clavero Ibarra, Pedro Luis, Mengual, Elisa, Arrasate, Montserrat, Hervás Stubbs, Sandra, Aymerich, María Soledad
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad San Jorge (USJ)
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/51878
Acceso en línea:https://hdl.handle.net/2454/51878
Access Level:acceso abierto
Palabra clave:Astrocyte
Inflammation
Microglia, Myeloid, Neurodegeneration
Parkinson&apos
s disease
Synuclein
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spelling Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's diseaseBasurco, LeyreAbellanas, Miguel ÁngelAyerra, LeyreConde, EnriqueVinueza-Gavilanes, RodrigoLuquin, EstherVales, AfricaVilas, AmaiaSan Martin-Uriz, PatxiTamayo Uria, IbonAlonso Roldán, MartaHernaez, MikelGonzález-Aseguinolaza, GloriaClavero Ibarra, Pedro LuisMengual, ElisaArrasate, MontserratHervás Stubbs, SandraAymerich, María SoledadAstrocyteInflammationMicroglia, Myeloid, NeurodegenerationParkinson&aposs diseaseSynucleinInflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated that the basal inflammatory tone differed between brain regions and, consequently, the reaction generated to a pro-inflammatory stimulus was different. In this study, we assessed the innate immune reaction in the midbrain and in the striatum using an experimental model of Parkinson's disease. An adeno-associated virus serotype 9 expressing the alpha-synuclein and mCherry genes or the mCherry gene was administered into the substantia nigra. Myeloid cells (CD11b(+)) and astrocytes (ACSA2(+)) were purified from the midbrain and striatum for bulk RNA sequencing. In the parkinsonian midbrain, CD11b(+) cells presented a unique anti-inflammatory transcriptomic profile that differed from degenerative microglia signatures described in experimental models for other neurodegenerative conditions. By contrast, striatal CD11b(+) cells showed a pro-inflammatory state and were similar to disease-associated microglia. In the midbrain, a prominent increase of infiltrated monocytes/macrophages was observed and, together with microglia, participated actively in the phagocytosis of dopaminergic neuronal bodies. Although striatal microglia presented a phagocytic transcriptomic profile, morphology and cell density was preserved and no active phagocytosis was detected. Interestingly, astrocytes presented a pro-inflammatory fingerprint in the midbrain and a low number of differentially displayed transcripts in the striatum. During alpha-synuclein-dependent degeneration, microglia and astrocytes experience context-dependent activation states with a different contribution to the inflammatory reaction. Our results point towards the relevance of selecting appropriate cell targets to design neuroprotective strategies aimed to modulate the innate immune system during the active phase of dopaminergic degeneration.Agencia Estatal de Investigación, Grant/Award Number: BFU2017-90043-P; Dirección General de Industria y Energia, Gobierno de Navarra. Proyectos Colaborativos, Grant/Award Numbers: PC 060-061, PC 192-193; Fundacion Gangoiti; Instituto de Salud Carlos III-FEDER, Grant/Award Numbers: PI20/01063, PI18/00556WileyCiencias de la SaludOsasun Zientziak2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2454/51878reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad San Jorge (USJ)Inglésinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-90043-Pinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01063info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00556info:eu-repo/grantAgreement/Gobierno de Navarra//PC060-061info:eu-repo/grantAgreement/Gobierno de Navarra//PC192-193© 2022 The Authors. GLIA published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/518782026-06-17T12:41:47Z
dc.title.none.fl_str_mv Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
title Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
spellingShingle Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
Basurco, Leyre
Astrocyte
Inflammation
Microglia, Myeloid, Neurodegeneration
Parkinson&apos
s disease
Synuclein
title_short Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
title_full Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
title_fullStr Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
title_full_unstemmed Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
title_sort Microglia and astrocyte activation is region-dependent in the α-synuclein mouse model of Parkinson's disease
dc.creator.none.fl_str_mv Basurco, Leyre
Abellanas, Miguel Ángel
Ayerra, Leyre
Conde, Enrique
Vinueza-Gavilanes, Rodrigo
Luquin, Esther
Vales, Africa
Vilas, Amaia
San Martin-Uriz, Patxi
Tamayo Uria, Ibon
Alonso Roldán, Marta
Hernaez, Mikel
González-Aseguinolaza, Gloria
Clavero Ibarra, Pedro Luis
Mengual, Elisa
Arrasate, Montserrat
Hervás Stubbs, Sandra
Aymerich, María Soledad
author Basurco, Leyre
author_facet Basurco, Leyre
Abellanas, Miguel Ángel
Ayerra, Leyre
Conde, Enrique
Vinueza-Gavilanes, Rodrigo
Luquin, Esther
Vales, Africa
Vilas, Amaia
San Martin-Uriz, Patxi
Tamayo Uria, Ibon
Alonso Roldán, Marta
Hernaez, Mikel
González-Aseguinolaza, Gloria
Clavero Ibarra, Pedro Luis
Mengual, Elisa
Arrasate, Montserrat
Hervás Stubbs, Sandra
Aymerich, María Soledad
author_role author
author2 Abellanas, Miguel Ángel
Ayerra, Leyre
Conde, Enrique
Vinueza-Gavilanes, Rodrigo
Luquin, Esther
Vales, Africa
Vilas, Amaia
San Martin-Uriz, Patxi
Tamayo Uria, Ibon
Alonso Roldán, Marta
Hernaez, Mikel
González-Aseguinolaza, Gloria
Clavero Ibarra, Pedro Luis
Mengual, Elisa
Arrasate, Montserrat
Hervás Stubbs, Sandra
Aymerich, María Soledad
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
dc.subject.none.fl_str_mv Astrocyte
Inflammation
Microglia, Myeloid, Neurodegeneration
Parkinson&apos
s disease
Synuclein
topic Astrocyte
Inflammation
Microglia, Myeloid, Neurodegeneration
Parkinson&apos
s disease
Synuclein
description Inflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated that the basal inflammatory tone differed between brain regions and, consequently, the reaction generated to a pro-inflammatory stimulus was different. In this study, we assessed the innate immune reaction in the midbrain and in the striatum using an experimental model of Parkinson's disease. An adeno-associated virus serotype 9 expressing the alpha-synuclein and mCherry genes or the mCherry gene was administered into the substantia nigra. Myeloid cells (CD11b(+)) and astrocytes (ACSA2(+)) were purified from the midbrain and striatum for bulk RNA sequencing. In the parkinsonian midbrain, CD11b(+) cells presented a unique anti-inflammatory transcriptomic profile that differed from degenerative microglia signatures described in experimental models for other neurodegenerative conditions. By contrast, striatal CD11b(+) cells showed a pro-inflammatory state and were similar to disease-associated microglia. In the midbrain, a prominent increase of infiltrated monocytes/macrophages was observed and, together with microglia, participated actively in the phagocytosis of dopaminergic neuronal bodies. Although striatal microglia presented a phagocytic transcriptomic profile, morphology and cell density was preserved and no active phagocytosis was detected. Interestingly, astrocytes presented a pro-inflammatory fingerprint in the midbrain and a low number of differentially displayed transcripts in the striatum. During alpha-synuclein-dependent degeneration, microglia and astrocytes experience context-dependent activation states with a different contribution to the inflammatory reaction. Our results point towards the relevance of selecting appropriate cell targets to design neuroprotective strategies aimed to modulate the innate immune system during the active phase of dopaminergic degeneration.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2454/51878
url https://hdl.handle.net/2454/51878
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-90043-P
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01063
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00556
info:eu-repo/grantAgreement/Gobierno de Navarra//PC060-061
info:eu-repo/grantAgreement/Gobierno de Navarra//PC192-193
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad San Jorge (USJ)
instname_str Universidad San Jorge (USJ)
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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