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

Date

2023

Authors

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

Director

Publisher

Wiley
Acceso abierto / Sarbide irekia
Artículo / Artikulua
Versión publicada / Argitaratu den bertsioa

Project identifier

AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-90043-P/ES/recolecta
ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01063/ES/recolecta
ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00556/ES/recolecta
Gobierno de Navarra//PC060-061
Gobierno de Navarra//PC192-193

Abstract

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.

Description

Keywords

Astrocyte, Inflammation, Microglia, Myeloid, Neurodegeneration, Parkinson's disease, Synuclein

Department

Ciencias de la Salud / Osasun Zientziak

Faculty/School

Degree

Doctorate program

item.page.cita

Basurco, L., Abellanas, M. A., Ayerra, L., Conde, E., Vinueza-Gavilanes, R., Luquin, E., Vales, A., Vilas, A., Martin-Uriz, P. S., Tamayo, I., Alonso, M. M., Hernaez, M., Gonzalez-Aseguinolaza, G., Clavero, P., Mengual, E., Arrasate, M., Hervás-Stubbs, S., Aymerich, M. (2023). Microglia and astrocyte activation is region-dependent in the a-synuclein mouse model of Parkinson's disease. Glia, 71(3), 571-587. https://doi.org/10.1002/glia.24295.

item.page.rights

© 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.

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