{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:00:50Z","timestamp":1782964850191,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). MS commonly affects the cerebellum causing acute and chronic symptoms. Cerebellar signs significantly contribute to clinical disability, and symptoms such as tremor, ataxia, and dysarthria are difficult to treat. Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies such as MS. In autopsy tissue from patients with MS, increased expression of FGF1, FGF2, FGF9, and FGFR1 was found in lesion areas. Recent research using mouse models has focused on regions such as the spinal cord, and data on the expression of FGF\/FGFR in the cerebellum are not available. In recent EAE studies, we detected that oligodendrocyte-specific deletion of FGFRs results in a milder disease course, less cellular infiltrates, and reduced neurodegeneration in the spinal cord. The objective of this study was to characterize the role of FGFR1 in oligodendrocytes in the cerebellum. Conditional deletion of FGFR1 in oligodendrocytes (Fgfr1ind\u2212\/\u2212) was achieved by tamoxifen application, EAE was induced using the MOG35-55 peptide. The cerebellum was analyzed by histology, immunohistochemistry, and western blot. At day 62 p.i., Fgfr1ind\u2212\/\u2212 mice showed less myelin and axonal degeneration compared to FGFR1-competent mice. Infiltration of CD3(+) T cells, Mac3(+) cells, B220(+) B cells and IgG(+) plasma cells in cerebellar white matter lesions (WML) was less in Fgfr1ind\u2212\/\u2212mice. There were no effects on the number of OPC or mature oligodendrocytes in white matter lesion (WML). Expression of FGF2 and FGF9 associated with less myelin and axonal degeneration, and of the pro-inflammatory cytokines IL-1\u03b2, IL-6, and CD200 was downregulated in Fgfr1ind\u2212\/\u2212 mice. The FGF\/FGFR signaling protein pAkt, BDNF, and TrkB were increased in Fgfr1ind\u2212\/\u2212 mice. These data suggest that cell-specific deletion of FGFR1 in oligodendrocytes has anti-inflammatory and neuroprotective effects in the cerebellum in the EAE disease model of MS.<\/jats:p>","DOI":"10.3390\/ijms22179495","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T21:59:45Z","timestamp":1630447185000},"page":"9495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oligodendrocyte-Specific Deletion of FGFR1 Reduces Cerebellar Inflammation and Neurodegeneration in MOG35-55-Induced EAE"],"prefix":"10.3390","volume":"22","author":[{"given":"Ranjithkumar","family":"Rajendran","sequence":"first","affiliation":[{"name":"Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9425-8579","authenticated-orcid":false,"given":"Vinothkumar","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Giraldo-Velasquez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sozialstiftung Bamberg, Buger Strasse 80, 96049 Bamberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fevronia-Foivi","family":"Megalofonou","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fynn","family":"Gurski","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Stadelmann","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Medical Center G\u00f6ttingen, Robert-Koch-Strasse 40, 37099 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9083-2916","authenticated-orcid":false,"given":"Srikanth","family":"Karnati","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, University of W\u00fcrzburg, Koellikerstrasse 6, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Berghoff","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00401-016-1631-4","article-title":"Multiple sclerosis: Experimental models and reality","volume":"133","author":"Lassmann","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/bs.pbr.2019.03.013","article-title":"Oligodendrocyte precursor cells as a therapeutic target for demyelinating diseases","volume":"245","author":"Skaper","year":"2019","journal-title":"Prog. 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