Publicaciones científicas

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

10-nov-2022 | Revista: Glia

Leyre Basurco 1 2, Miguel Angel Abellanas 1 2, Leyre Ayerra 1 2, Enrique Conde 3, Rodrigo Vinueza-Gavilanes 2, Esther Luquin 4, Africa Vales 5, Amaya Vilas 6, Patxi San Martin-Uriz 6, Ibon Tamayo 7, Marta M Alonso 8 9, Mikel Hernaez 7, Gloria Gonzalez-Aseguinolaza 5 9, Pedro Clavero 10, Elisa Mengual 4, Montserrat Arrasate 2 9, Sandra Hervás-Stubbs 3 9, Maria S Aymerich 1 2 8 9


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 α-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 α-synuclein-dependent degeneration, microglia and astrocytes experience context-dependent activation states with a different contribution to the inflammatory reaction. Our results point toward the relevance of selecting appropriate cell targets to design neuroprotective strategies to modulate the innate immune system during the active phase of dopaminergic degeneration.

Keywords: Parkinson's disease; astrocyte; inflammation; microglia; myeloid; neurodegeneration; synuclein.

CITA DEL ARTÍCULO Glia. 2022 Nov 10. doi: 10.1002/glia.24295. Online ahead of print.

Nuestros autores

Leyre Basurco Gogorcena
Enrique Conde Gallastegi
África Vales Aranguren
Dr. Patxi San Martín Uriz
Investigador Adscrito a Proyecto Programa de Investigación de Hemato-Oncología
Ibon Tamayo Uría
Colaborador de Investigación Plataforma Bioinformática
Dr. Mikel Hernáez Arrazola
Director | Investigador principal Plataforma Bioinformática
Dra. Montserrat Arrasate Iragui
Rodrigo Vinueza Gavilanes
Dra. Sandra Hervás Stubbs
Investigadora | Investigadora principal Programa de Investigación de Inmunología e Inmunoterapia
Dr. Patxi San Martín Uriz
Investigador Adscrito a Proyecto Programa de Investigación de Hemato-Oncología