TY  - JOUR
A1  - Kamali, Salar
A1  - Rajendran, Ranjithkumar
A1  - Stadelmann, Christine
A1  - Karnati, Srikanth
A1  - Rajendran, Vinothkumar
A1  - Giraldo‐Velasquez, Mario
A1  - Berghoff, Martin
T1  - Oligodendrocyte‐specific deletion of FGFR2 ameliorates MOG\(_{35-55}\)‐induced EAE through ERK and Akt signalling
JF  - Brain Pathology
N2  - Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies including multiple sclerosis (MS). In our recent study, oligodendrocyte‐specific deletion of FGFR1 resulted in a milder disease course, less inflammation, reduced myelin and axon damage in EAE. The objective of this study was to elucidate the role of oligodendroglial FGFR2 in MOG\(_{35-55}\)‐induced EAE. Oligodendrocyte‐specific knockout of FGFR2 (Fgfr2\(^{ind-/-}\)) was achieved by application of tamoxifen; EAE was induced using the MOG\(_{35-55}\) peptide. EAE symptoms were monitored over 62 days. Spinal cord tissue was analysed by histology, immunohistochemistry and western blot. Fgfr2\(^{ind-/-}\) mice revealed a milder disease course, less myelin damage and enhanced axonal density. The number of oligodendrocytes was not affected in demyelinated areas. However, protein expression of FGFR2, FGF2 and FGF9 was downregulated in Fgfr2\(^{ind-/-}\) mice. FGF/FGFR dependent signalling proteins were differentially regulated; pAkt was upregulated and pERK was downregulated in Fgfr2\(^{ind-/-}\) mice. The number of CD3(+) T cells, Mac3(+) cells and B220(+) B cells was less in demyelinated lesions of Fgfr2\(^{ind-/-}\) mice. Furthermore, expression of IL‐1β, TNF‐α and CD200 was less in Fgfr2\(^{ind-/-}\) mice than controls. Fgfr2ind−/− mice showed an upregulation of PLP and downregulation of the remyelination inhibitors SEMA3A and TGF‐β expression. These data suggest that cell‐specific deletion of FGFR2 in oligodendrocytes has anti‐inflammatory and neuroprotective effects accompanied by changes in FGF/FGFR dependent signalling, inflammatory cytokines and expression of remyelination inhibitors. Thus, FGFRs in oligodendrocytes may represent potential targets for the treatment of inflammatory and demyelinating diseases including MS.
KW  - experimental autoimmune encephalomyelitis
KW  - FGF/FGFR signalling
KW  - multiple sclerosis
KW  - oligodendrocytes
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224354
VL  - 31
SP  - 297
EP  - 311
ER  - 
TY  - JOUR
A1  - Vogelsang, Anna
A1  - Eichler, Susann
A1  - Huntemann, Niklas
A1  - Masanneck, Lars
A1  - Böhnlein, Hannes
A1  - Schüngel, Lisa
A1  - Willison, Alice
A1  - Loser, Karin
A1  - Nieswandt, Bernhard
A1  - Kehrel, Beate E.
A1  - Zarbock, Alexander
A1  - Göbel, Kerstin
A1  - Meuth, Sven G.
T1  - Platelet inhibition by low-dose acetylsalicylic acid reduces neuroinflammation in an animal model of multiple sclerosis
JF  - International Journal of Molecular Sciences
N2  - Aside from the established immune-mediated etiology of multiple sclerosis (MS), compelling evidence implicates platelets as important players in disease pathogenesis. Specifically, numerous studies have highlighted that activated platelets promote the central nervous system (CNS)-directed adaptive immune response early in the disease course. Platelets, therefore, present a novel opportunity for modulating the neuroinflammatory process that characterizes MS. We hypothesized that the well-known antiplatelet agent acetylsalicylic acid (ASA) could inhibit neuroinflammation by affecting platelets if applied at low-dose and investigated its effect during experimental autoimmune encephalomyelitis (EAE) as a model to study MS. We found that oral administration of low-dose ASA alleviates symptoms of EAE accompanied by reduced inflammatory infiltrates and less extensive demyelination. Remarkably, the percentage of CNS-infiltrated CD4\(^+\) T cells, the major drivers of neuroinflammation, was decreased to 40.98 ± 3.28% in ASA-treated mice compared to 56.11 ± 1.46% in control animals at the disease maximum as revealed by flow cytometry. More interestingly, plasma levels of thromboxane A\(_2\) were decreased, while concentrations of platelet factor 4 and glycoprotein VI were not affected by low-dose ASA treatment. Overall, we demonstrate that low-dose ASA could ameliorate the platelet-dependent neuroinflammatory response in vivo, thus indicating a potential treatment approach for MS.
KW  - acetylsalicylic acid
KW  - experimental autoimmune encephalomyelitis
KW  - platelets
KW  - multiple sclerosis
KW  - thromboxane
KW  - glycoprotein VI
KW  - platelet factor 4
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284535
SN  - 1422-0067
VL  - 22
IS  - 18
ER  -