{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:34:42Z","timestamp":1788798882687,"version":"build-2803163510"},"reference-count":66,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["39087428"],"award-info":[{"award-number":["39087428"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010570","name":"Nieders\u00e4chsisches Ministerium f\u00fcr Wissenschaft und Kultur","doi-asserted-by":"publisher","award":["398066876"],"award-info":[{"award-number":["398066876"]}],"id":[{"id":"10.13039\/501100010570","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Demyelination in the central nervous system (CNS) is a hallmark of many neurodegenerative diseases such as multiple sclerosis (MS) and others. Here, we studied astrocytes during de\u2010 and remyelination in the cuprizone mouse model. To this end, we exploited the ribosomal tagging (RiboTag) technology that is based on Cre\u2010mediated cell type\u2010selective HA\u2010tagging of ribosomes. Analyses were performed in the corpus callosum of GFAP\u2010Cre<jats:sup>+\/\u2212<\/jats:sup>Rpl22<jats:sup>HA\/wt<\/jats:sup> mice 5\u2009weeks after cuprizone feeding, at the peak of demyelination, and 0.5 and 2\u2009weeks after cuprizone withdrawal, when remyelination and tissue repair is initiated. After 5\u2009weeks of cuprizone feeding, reactive astrocytes showed inflammatory signatures with enhanced expression of genes that modulate leukocyte migration (<jats:italic>Tlr2<\/jats:italic>, <jats:italic>Cd86<\/jats:italic>, <jats:italic>Parp14<\/jats:italic>) and they produced the chemokine CXCL10, as verified by histology. Furthermore, demyelination\u2010induced reactive astrocytes expressed numerous ligands including <jats:italic>Cx3cl1<\/jats:italic>, <jats:italic>Csf1<\/jats:italic>, <jats:italic>Il34<\/jats:italic>, and <jats:italic>Gas6<\/jats:italic> that act on homeostatic as well as activated microglia and thus potentially mediate activation and recruitment of microglia and enhancement of their phagocytotic activity. During early remyelination, HA\u2010tagged cells displayed reduced inflammatory response signatures, as indicated by shutdown of CXCL10 production, and enhanced expression of osteopontin (SPP1) as well as of factors that are relevant for tissue remodeling (<jats:italic>Timp1<\/jats:italic>), regeneration and axonal repair. During late remyelination, the signatures shifted towards resolving inflammation by active suppression of lymphocyte activation and differentiation and support of glia cell differentiation. In conclusion, we detected highly dynamic astroglial transcriptomic signatures in the cuprizone model, which reflects excessive communication among glia cells and highlights different astrocyte functions during neurodegeneration and regeneration.<\/jats:p>","DOI":"10.1002\/glia.24440","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T07:01:20Z","timestamp":1689577280000},"page":"2573-2590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Dynamics of reactive astrocytes fosters tissue regeneration after cuprizone\u2010induced demyelination"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9068-4234","authenticated-orcid":false,"given":"Lara\u2010Jasmin","family":"Schr\u00f6der","sequence":"first","affiliation":[{"name":"Department of Neurology Hannover Medical School  Hannover Germany"},{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research A Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"},{"name":"Center for Systems Neuroscience University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-2461","authenticated-orcid":false,"given":"Felix","family":"Mulenge","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research A Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-459X","authenticated-orcid":false,"given":"Andreas","family":"Pavlou","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research A Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Skripuletz","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Stangel","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School  Hannover Germany"},{"name":"Center for Systems Neuroscience University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0438-2339","authenticated-orcid":false,"given":"Viktoria","family":"Gudi","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-9564","authenticated-orcid":false,"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research A Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"},{"name":"Center for Systems Neuroscience University of Veterinary Medicine Hannover  Hannover Germany"},{"name":"Cluster of Excellence RESIST (EXC 2155) Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.14.5100-5113.2002"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-020-01771-w"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-013-9380-9"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017727"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3599"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1230-6"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.103778"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.12.006"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062960"},{"key":"e_1_2_12_13_1","first-page":"1025","article-title":"Treatment of Multiple Sclerosis","volume":"28","author":"Cross A.","year":"2022","journal-title":"Treatment of Multiple Sclerosis. Continuum (Minneap Minn)"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-022-02096-y"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2480"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020594"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.09.023"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102194"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.995477"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abc9165"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1194637"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102261"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00073"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.06.005"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-018-0228-4"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112293"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00913-5"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1415"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23937"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbacli.2015.01.003"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141656"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2017.08.002"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232416093"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.12.026"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0091-5"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.16111286"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.3.262"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102188"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2001.tb00385.x"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5474-10.2011"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1310-7"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011811-132443"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23214"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11053-8"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907143106"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.12.002"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2003.12.014"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24148"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws262"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.32552\/2021.ActaMedica.498"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.11.030"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.2174\/2772432817666220412110720"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(02)00105-3"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.139"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/274168a0"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021857"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.077214"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015748"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1514-09.2009"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2360"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/87945"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00584-2"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T09:33:23Z","timestamp":1693906403000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.24440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,17]]},"references-count":66,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/glia.24440"],"URL":"https:\/\/doi.org\/10.1002\/glia.24440","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,17]]},"assertion":[{"value":"2023-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}