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The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes\u2019 transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize \u201castrocyte reactivity\u201d. Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS.<\/jats:p>","DOI":"10.3390\/cells12202484","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T02:54:43Z","timestamp":1697684083000},"page":"2484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0211-3274","authenticated-orcid":false,"given":"Sofia Pereira","family":"das Neves","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s PT Government Associate Laboratory, 4806-909 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3249-0035","authenticated-orcid":false,"given":"Jo\u00e3o Carlos","family":"Sousa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s PT Government Associate Laboratory, 4806-909 Guimar\u00e3es, Portugal"}]},{"given":"Ricardo","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"NeuroSpin, CEA, Paris-Saclay University, Centre d\u2019\u00e9tudes de Saclay, B\u00e2timent 145, 91191 Gif-sur-Yvette, France"}]},{"given":"Fuying","family":"Gao","sequence":"additional","affiliation":[{"name":"Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}]},{"given":"Giovanni","family":"Coppola","sequence":"additional","affiliation":[{"name":"Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}]},{"given":"Sebatien","family":"M\u00e9riaux","sequence":"additional","affiliation":[{"name":"NeuroSpin, CEA, Paris-Saclay University, Centre d\u2019\u00e9tudes de Saclay, B\u00e2timent 145, 91191 Gif-sur-Yvette, France"}]},{"given":"Fawzi","family":"Boumezbeur","sequence":"additional","affiliation":[{"name":"NeuroSpin, CEA, Paris-Saclay University, Centre d\u2019\u00e9tudes de Saclay, B\u00e2timent 145, 91191 Gif-sur-Yvette, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8755-5126","authenticated-orcid":false,"given":"Nuno","family":"Sousa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s PT Government Associate Laboratory, 4806-909 Guimar\u00e3es, Portugal"},{"name":"Clinical Academic Center, 4710-243 Braga, Portugal"}]},{"given":"Jo\u00e3o Jos\u00e9","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s PT Government Associate Laboratory, 4806-909 Guimar\u00e3es, Portugal"},{"name":"Clinical Academic Center, 4710-243 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, Campus Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s PT Government Associate Laboratory, 4806-909 Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","article-title":"Multiple Sclerosis Pathology","volume":"8","author":"Lassmann","year":"2018","journal-title":"Cold Spring Harb. 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Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/08916939809003872","article-title":"Induction of a multiple sclerosis-like disease in mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein","volume":"28","author":"Slavin","year":"1998","journal-title":"Autoimmunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.23.021704.115707","article-title":"Immunology of multiple sclerosis","volume":"23","author":"Sospedra","year":"2005","journal-title":"Ann. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/j.1600-0463.2011.02794.x","article-title":"Experimental autoimmune encephalomyelitis\u2014Achievements and prospective advances","volume":"119","author":"Batoulis","year":"2011","journal-title":"APMIS"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1038\/nprot.2006.285","article-title":"Active induction of experimental allergic encephalomyelitis","volume":"1","author":"Stromnes","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1476-5381.2011.01302.x","article-title":"Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)","volume":"164","author":"Constantinescu","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jneuroim.2007.06.016","article-title":"MP4- and MOG:35-55-induced EAE in C57BL\/6 mice differentially targets brain, spinal cord and cerebellum","volume":"189","author":"Kuerten","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/nn.3168","article-title":"Animal models of multiple sclerosis: The good, the bad and the bottom line","volume":"15","author":"Ransohoff","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104242","DOI":"10.1016\/j.cellimm.2020.104242","article-title":"Sex differences in EAE reveal common and distinct cellular and molecular components","volume":"359","author":"Wiedrick","year":"2021","journal-title":"Cell Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Holt, L.M., and Olsen, M.L. (2016). Novel Applications of Magnetic Cell Sorting to Analyze Cell-Type Specific Gene and Protein Expression in the Central Nervous System. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150290"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D712","DOI":"10.1093\/nar\/gkq1156","article-title":"ConsensusPathDB: Toward a more complete picture of cell biology","volume":"39","author":"Kamburov","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D623","DOI":"10.1093\/nar\/gkn698","article-title":"ConsensusPathDB--a database for integrating human functional interaction networks","volume":"37","author":"Kamburov","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1093\/bioinformatics\/btr390","article-title":"Simple Neurite Tracer: Open source software for reconstruction, visualization and analysis of neuronal processes","volume":"27","author":"Longair","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1007\/s00429-016-1316-8","article-title":"Employing an open-source tool to assess astrocyte tridimensional structure","volume":"222","author":"Tavares","year":"2017","journal-title":"Brain Struct. Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"863","DOI":"10.3389\/fpsyg.2013.00863","article-title":"Calculating and reporting effect sizes to facilitate cumulative science: A practical primer for t-tests and ANOVAs","volume":"4","author":"Lakens","year":"2013","journal-title":"Front. Psychol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1002\/glia.23140","article-title":"Anti-ACSA-2 defines a novel monoclonal antibody for prospective isolation of living neonatal and adult astrocytes","volume":"65","author":"Kantzer","year":"2017","journal-title":"Glia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8874","DOI":"10.1074\/jbc.M116.765313","article-title":"An immunoaffinity-based method for isolating ultrapure adult astrocytes based on ATP1B2 targeting by the ACSA-2 antibody","volume":"292","author":"Batiuk","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4049\/jimmunol.169.1.117","article-title":"Pertussis toxin modulates the immune response to neuroantigens injected in incomplete Freund\u2019s adjuvant: Induction of Th1 cells and experimental autoimmune encephalomyelitis in the presence of high frequencies of Th2 cells","volume":"169","author":"Hofstetter","year":"2002","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.4049\/jimmunol.178.4.2212","article-title":"Peripheral tolerance induction using ethylenecarbodiimide-fixed APCs uses both direct and indirect mechanisms of antigen presentation for prevention of experimental autoimmune encephalomyelitis","volume":"178","author":"Turley","year":"2007","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/457675a","article-title":"Neuroscience: Glia\u2014More than just brain glue","volume":"457","author":"Allen","year":"2009","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ddmod.2006.11.004","article-title":"Animal models of multiple sclerosis","volume":"3","author":"Wekerle","year":"2006","journal-title":"Drug Discov. Today Dis. Models"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1089\/jir.2011.0072","article-title":"The immune pathogenesis of experimental autoimmune encephalomyelitis: Lessons learned for multiple sclerosis?","volume":"31","author":"Kuerten","year":"2011","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_32","first-page":"420","article-title":"Metabolic reprograming in macrophage polarization","volume":"5","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/bph.13139","article-title":"Microglial M1\/M2 polarization and metabolic states","volume":"173","author":"Orihuela","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/j.cell.2019.11.016","article-title":"Metabolic Control of Astrocyte Pathogenic Activity via cPLA2-MAVS","volume":"179","author":"Chao","year":"2019","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/nm.3681","article-title":"Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation","volume":"20","author":"Mayo","year":"2014","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1742-2094-5-20","article-title":"Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysis","volume":"5","author":"Mueller","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E302","DOI":"10.1073\/pnas.1716032115","article-title":"Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes","volume":"115","author":"Itoh","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10010","DOI":"10.1038\/s41598-019-46232-6","article-title":"The astrocyte transcriptome in EAE optic neuritis shows complement activation and reveals a sex difference in astrocytic C3 expression","volume":"9","author":"Tassoni","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sevastou, I., Pryce, G., Baker, D., and Selwood, D.L. (2016). Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157754"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103758","DOI":"10.1016\/j.mcn.2022.103758","article-title":"Dimethyl itaconate reprograms neurotoxic to neuroprotective primary astrocytes through the regulation of NLRP3 inflammasome and NRF2\/HO-1 pathways","volume":"122","author":"Khadem","year":"2022","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1002\/glia.23835","article-title":"The metabolic response to inflammation in astrocytes is regulated by nuclear factor-kappa B signaling","volume":"68","author":"Robb","year":"2020","journal-title":"Glia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0022-510X(79)90142-4","article-title":"A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis","volume":"41","author":"Allen","year":"1979","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.1750-3639.2003.tb00485.x","article-title":"Molecular changes in normal appearing white matter in multiple sclerosis are characteristic of neuroprotective mechanisms against hypoxic insult","volume":"13","author":"Graumann","year":"2003","journal-title":"Brain Pathol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/20\/2484\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:09:31Z","timestamp":1760130571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/20\/2484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,19]]},"references-count":43,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["cells12202484"],"URL":"https:\/\/doi.org\/10.3390\/cells12202484","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,19]]}}}