{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:27:03Z","timestamp":1761294423907,"version":"build-2065373602"},"reference-count":104,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T00:00:00Z","timestamp":1642896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/NEU-NMC\/3648\/2014","PD\/BD\/127828\/2016","PD\/BD\/114120\/2015","PTDC\/MED-NEU\/31318\/2017","UIDB\/50026\/2020","UIDP\/50026\/2020"],"award-info":[{"award-number":["PTDC\/NEU-NMC\/3648\/2014","PD\/BD\/127828\/2016","PD\/BD\/114120\/2015","PTDC\/MED-NEU\/31318\/2017","UIDB\/50026\/2020","UIDP\/50026\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"COMPETE-FEDER","award":["POCI-01-0145-FEDER-016818","POCI-01-0145- FEDER-030647"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016818","POCI-01-0145- FEDER-030647"]}]},{"name":"Portuguese Platform of Bioimaging","award":["PPBI-POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["PPBI-POCI-01-0145-FEDER-022122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>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\u2013Joseph 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.<\/jats:p>","DOI":"10.3390\/biomedicines10020237","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T20:32:52Z","timestamp":1642969972000},"page":"237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Profiling Microglia in a Mouse Model of Machado\u2013Joseph Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Ana Bela","family":"Campos","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9680-4027","authenticated-orcid":false,"given":"Sara","family":"Duarte-Silva","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1561-2897","authenticated-orcid":false,"given":"Bruno","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Informatics, ALGORITMI Center, University of Minho, 4710-057 Braga, Portugal"}]},{"given":"Sofia Pereira","family":"das Neves","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3612-1870","authenticated-orcid":false,"given":"Fernanda","family":"Marques","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-5996","authenticated-orcid":false,"given":"Andreia","family":"Teixeira-Castro","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Andreia","family":"Neves-Carvalho","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Daniela","family":"Monteiro-Fernandes","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1093-6545","authenticated-orcid":false,"given":"Camila Cabral","family":"Portugal","sequence":"additional","affiliation":[{"name":"Glial Cell Biology Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Instituto de Biologia Molecular e Celular (IBMC), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6882-5020","authenticated-orcid":false,"given":"Renato","family":"Socodato","sequence":"additional","affiliation":[{"name":"Glial Cell Biology Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Instituto de Biologia Molecular e Celular (IBMC), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-6281","authenticated-orcid":false,"given":"Teresa","family":"Summavielle","sequence":"additional","affiliation":[{"name":"Addiction Biology Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Instituto de Biologia Molecular e Celular (IBMC), University of Porto, 4200-135 Porto, Portugal"},{"name":"ESS.PP, Escola Superior de Sa\u00fade do Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-1641","authenticated-orcid":false,"given":"Ant\u00f3nio Francisco","family":"Ambr\u00f3sio","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Univiversity of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), Univiversity of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"given":"Jo\u00e3o Bettencourt","family":"Relvas","sequence":"additional","affiliation":[{"name":"Glial Cell Biology Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Instituto de Biologia Molecular e Celular (IBMC), University of Porto, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0920-6350","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Maciel","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s, PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12974-018-1195-4","article-title":"RNA sequencing analysis reveals quiescent microglia isolation methods from postnatal mouse brains and limitations of BV2 cells","volume":"15","author":"He","year":"2018","journal-title":"J. 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