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Oligodendrocyte-specific deletion of FGFR1 reduces cerebellar inflammation and neurodegeneration in MOG\(_{35-55}\)-induced EAE

Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-284296
  • 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 inMultiple 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 (Fgfr1\(^{ind−/−}\) was achieved by tamoxifen application, EAE was induced using the MOG\(_{35-55}\) peptide. The cerebellum was analyzed by histology, immunohistochemistry, and western blot. At day 62 p.i., Fgfr1\(^{ind−/−}\) 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 Fgfr1\(^{ind−/−}\)mice. 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-1β, IL-6, and CD200 was downregulated in Fgfr1\(^{ind−/−}\) mice. The FGF/FGFR signaling protein pAkt, BDNF, and TrkB were increased in Fgfr1\(^{ind−/−}\) 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.zeige mehrzeige weniger

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Autor(en): Ranjithkumar Rajendran, Vinothkumar Rajendran, Mario Giraldo-Velasquez, Fevronia-Foivi Megalofonou, Fynn Gurski, Christine Stadelmann, Srikanth Karnati, Martin Berghoff
URN:urn:nbn:de:bvb:20-opus-284296
Dokumentart:Artikel / Aufsatz in einer Zeitschrift
Institute der Universität:Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Sprache der Veröffentlichung:Englisch
Titel des übergeordneten Werkes / der Zeitschrift (Englisch):International Journal of Molecular Sciences
ISSN:1422-0067
Erscheinungsjahr:2021
Band / Jahrgang:22
Heft / Ausgabe:17
Aufsatznummer:9495
Originalveröffentlichung / Quelle:International Journal of Molecular Sciences (2021) 22:17, 9495. https://doi.org/10.3390/ijms22179495
DOI:https://doi.org/10.3390/ijms22179495
Allgemeine fachliche Zuordnung (DDC-Klassifikation):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Freie Schlagwort(e):EAE; FGFR1; MS; cerebellum; demyelination; inflammation; oligodendrocytes
Datum der Freischaltung:28.06.2023
Datum der Erstveröffentlichung:31.08.2021
Lizenz (Deutsch):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International