Profiling Microglia in a Mouse Model of Machado-Joseph Disease

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Campos, AB (Author) Other; Duarte Silva, S (Author) Other; Fernandes, B (Author) Other; das Neves, SP (Author) Other; Marques, F (Author) Other; Teixeira Castro, A (Author) Other; Neves Carvalho, A (Author) Other; Monteiro Fernandes, D (Author) Other; Portugal, CC (Author) Other; Socodato, R (Author) Other; Summavielle, T (Author) Other; Ambrosio, AF (Author) Other; Relvas, JB (Author) FMUP; Maciel, P (Author) Other

Journal

Title: Biomedicines

Vol. 13

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00W-1WC

DOI: 10.3390/biomedicines10020237

Abstract (EN): Microglia have been increasingly implicated in neurodegenerative diseases (NDs), and specific disease associated microglia (DAM) profiles have been defined for several of these NDs. Yet, the microglial profile in Machado-Joseph disease (MJD) remains unexplored. Here, we characterized the profile of microglia in the CMVMJD135 mouse model of MJD. This characterization was performed using primary microglial cultures and microglial cells obtained from disease-relevant brain regions of neonatal and adult CMVMJD135 mice, respectively. Machine learning models were implemented to identify potential clusters of microglia based on their morphological features, and an RNA-sequencing analysis was performed to identify molecular perturbations and potential therapeutic targets. Our findings reveal morphological alterations that point to an increased activation state of microglia in CMVMJD135 mice and a disease-specific transcriptional profile of MJD microglia, encompassing a total of 101 differentially expressed genes, with enrichment in molecular pathways related to oxidative stress, immune response, cell proliferation, cell death, and lipid metabolism. Overall, these results allowed us to define the cellular and molecular profile of MJD-associated microglia and to identify genes and pathways that might represent potential therapeutic targets for this disorder.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 27