{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:28:02Z","timestamp":1783441682093,"version":"3.54.6"},"reference-count":83,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Spanish Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["PI17\/00093"],"award-info":[{"award-number":["PI17\/00093"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Spanish Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["PI20\/00147"],"award-info":[{"award-number":["PI20\/00147"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Spanish Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["CP18\/00034"],"award-info":[{"award-number":["CP18\/00034"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union","award":["PI17\/00093"],"award-info":[{"award-number":["PI17\/00093"]}]},{"name":"European Union","award":["PI20\/00147"],"award-info":[{"award-number":["PI20\/00147"]}]},{"name":"European Union","award":["CP18\/00034"],"award-info":[{"award-number":["CP18\/00034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>By means of a proteomic approach, we assessed the pathways involved in cerebellar neurodegeneration in a mouse model (Harlequin, Hq) of mitochondrial disorder. A differential proteomic profile study (iTRAQ) was performed in cerebellum homogenates of male Hq and wild-type (WT) mice 8 weeks after the onset of clear symptoms of ataxia in the Hq mice (aged 5.2 \u00b1 0.2 and 5.3 \u00b1 0.1 months for WT and Hq, respectively), followed by a biochemical validation of the most relevant changes. Additional groups of 2-, 3- and 6-month-old WT and Hq mice were analyzed to assess the disease progression on the proteins altered in the proteomic study. The proteomic analysis showed that beyond the expected deregulation of oxidative phosphorylation, the cerebellum of Hq mice showed a marked astroglial activation together with alterations in Ca2+ homeostasis and neurotransmission, with an up- and downregulation of GABAergic and glutamatergic neurotransmission, respectively, and the downregulation of cerebellar \u201clong-term depression\u201d, a synaptic plasticity phenomenon that is a major player in the error-driven learning that occurs in the cerebellar cortex. Our study provides novel insights into the mechanisms associated with cerebellar degeneration in the Hq mouse model, including a complex deregulation of neuroinflammation, oxidative phosphorylation and glutamate, GABA and amino acids\u2019 metabolism<\/jats:p>","DOI":"10.3390\/ijms241310973","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:06:37Z","timestamp":1688141197000},"page":"10973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pathophysiology of Cerebellar Degeneration in Mitochondrial Disorders: Insights from the Harlequin Mouse"],"prefix":"10.3390","volume":"24","author":[{"given":"Miguel","family":"Fern\u00e1ndez de la Torre","sequence":"first","affiliation":[{"name":"Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Fiuza-Luces","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Laine-Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aitor","family":"Delmiro","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019), 28041 Madrid, Spain"},{"name":"Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, 28029 Madrid, Spain"},{"name":"Servicio de Bioqu\u00edmica Cl\u00ednica, Hospital Universitario \u201c12 de Octubre\u201d, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Arenas","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019), 28041 Madrid, Spain"},{"name":"Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-772X","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019), 28041 Madrid, Spain"},{"name":"Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, 28029 Madrid, Spain"},{"name":"Servicio de Gen\u00e9tica, Hospital Universitario \u201c12 de Octubre\u201d, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Lucia","sequence":"additional","affiliation":[{"name":"Faculty of Sports Sciences, European University of Madrid, 28670 Madrid, Spain"},{"name":"Spanish Network for Biomedical Research in Fragility and Healthy Aging (CIBERFES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5408-7189","authenticated-orcid":false,"given":"Mar\u00eda","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019), 28041 Madrid, Spain"},{"name":"Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. 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