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Scientific Microscopy Platform","award":["(PTDC\/NEUNMC\/3648\/2014)"],"award-info":[{"award-number":["(PTDC\/NEUNMC\/3648\/2014)"]}]},{"name":"ICVS Scientific Microscopy Platform","award":["(PTDC\/MED-OUT\/31987\/2017)"],"award-info":[{"award-number":["(PTDC\/MED-OUT\/31987\/2017)"]}]},{"name":"ICVS Scientific Microscopy Platform","award":["(PD\/BD\/127828\/2016)"],"award-info":[{"award-number":["(PD\/BD\/127828\/2016)"]}]},{"name":"ICVS Scientific Microscopy Platform","award":["(2020.03898.CEECIND)"],"award-info":[{"award-number":["(2020.03898.CEECIND)"]}]},{"name":"ICVS Scientific Microscopy Platform","award":["UIDB\/50026\/2020"],"award-info":[{"award-number":["UIDB\/50026\/2020"]}]},{"name":"ICVS Scientific Microscopy Platform","award":["UIDP\/50026\/2020"],"award-info":[{"award-number":["UIDP\/50026\/2020"]}]},{"name":"ICVS Scientific Microscopy Platform","award":["(POCI-01-0145-FEDER-016818)"],"award-info":[{"award-number":["(POCI-01-0145-FEDER-016818)"]}]},{"name":"ICVS 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While most research in NDs has been following a neuron-centric point of view, microglia are now recognized as crucial in the brain. Previous work revealed alterations that point to an increased activation state of microglia in the brain of CMVMJD135 mice, a MJD mouse model that replicates the motor symptoms and neuropathology of the human condition. Here, we investigated the extent to which microglia are actively contributing to MJD pathogenesis and symptom progression. For this, we used PLX3397 to reduce the number of microglia in the brain of CMVMJD135 mice. In addition, a set of statistical and machine learning models were further implemented to analyze the impact of PLX3397 on the morphology of the surviving microglia. Then, a battery of behavioral tests was used to evaluate the impact of microglial depletion on the motor phenotype of CMVMJD135 mice. Although PLX3397 treatment substantially reduced microglia density in the affected brain regions, it did not affect the motor deficits seen in CMVMJD135 mice. In addition to reducing the number of microglia, the treatment with PLX3397 induced morphological changes suggestive of activation in the surviving microglia, the microglia of wild-type animals becoming similar to those of CMVMJD135 animals. These results suggest that microglial cells are not key contributors for MJD progression. Furthermore, the impact of PLX3397 on microglial activation should be taken into account in the interpretation of findings of ND modification seen upon treatment with this CSF1R inhibitor.<\/jats:p>","DOI":"10.3390\/cells11132022","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T10:39:13Z","timestamp":1656153553000},"page":"2022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Microglial Depletion Has No Impact on Disease Progression in a Mouse Model of Machado\u2013Joseph Disease"],"prefix":"10.3390","volume":"11","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Coimbra","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Campos","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1212\/WNL.28.7.703","article-title":"Autosomal dominant system degeneration in Portuguese families of the Azores Islands. 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