Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/78469
Título: | Profiling microglia in a mouse model of Machado-Joseph disease |
Autor(es): | Campos, Ana Bela Silva, Sara Carina Duarte Fernandes, B. Neves, Sofia Pereira Marques, Fernanda Castro, Andreia Cristiana Teixeira Carvalho, Andreia Alexandra Neves Fernandes, Daniela Monteiro Portugal, Camila Cabral Socodato, Renato Summavielle, Teresa Ambrósio, António Francisco Relvas, João Bettencourt Maciel, P. |
Palavras-chave: | Microglia Machado-Joseph disease Cell morphology RNA-sequencing Machine learning |
Data: | 23-Jan-2022 |
Editora: | Multidisciplinary Digital Publishing Institute (MDPI) |
Revista: | Biomedicines |
Citação: | Campos, A.B.; Duarte-Silva, S.; Fernandes, B.; das Neves, S.P.; Marques, F.; Teixeira-Castro, A.; Neves-Carvalho, A.; Monteiro-Fernandes, D.; Portugal, C.C.; Socodato, R.; Summavielle, T.; Ambrósio, A.F.; Relvas, J.B.; Maciel, P. Profiling Microglia in a Mouse Model of Machado–Joseph Disease. Biomedicines 2022, 10, 237. https://doi.org/10.3390/biomedicines10020237 |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/78469 |
DOI: | 10.3390/biomedicines10020237 |
e-ISSN: | 2227-9059 |
Versão da editora: | https://www.mdpi.com/2227-9059/10/2/237 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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biomedicines-10-00237-v2.pdf | 14,27 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons