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

• DOI: 10.1002/glia.24295
• Publication Date: 2022-11-10T09:07:39Z
• Authors: Leyre Basurco; Miguel Angel Abel...; Leyre Ayerra; Enrique Conde; Rodrigo Vinueza‐G...; Esther Luquin; Africa Vales; Amaya Vilas; Patxi San Martin‐...; Ibon Tamayo; Marta M. Alonso; Mikel Hernaez; Gloria Gonzalez‐A...; Pedro Clavero; Elisa Mengual; Montserrat Arrasate; Sandra Hervás‐Stubbs; Maria S. Aymerich
• Keywords: Astrogliosis

Inflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated the basal inflammatory tone differed between brain regions and, consequently, reaction generated pro-inflammatory stimulus was different. In this study, assessed innate immune midbrain and striatum using an experimental model of Parkinson's disease. An adeno-associated virus serotype 9 expressing α-synuclein mCherry genes or gene administered into substantia nigra. Myeloid cells (CD11b+ ) astrocytes (ACSA2+ were purified from for bulk RNA sequencing. parkinsonian midbrain, CD11b+ presented unique anti-inflammatory transcriptomic profile degenerative microglia signatures described models other conditions. By contrast, striatal showed state similar disease-associated microglia. prominent increase infiltrated monocytes/macrophages observed together with microglia, participated actively phagocytosis dopaminergic bodies. Although phagocytic profile, morphology cell density preserved no active detected. Interestingly, fingerprint low number differentially displayed transcripts striatum. During α-synuclein-dependent degeneration, experience context-dependent activation states different contribution reaction. Our results point towards relevance selecting appropriate targets design neuroprotective strategies aimed modulate system during phase degeneration.