TY  - JOUR
A1  - Karnati, Srikanth
A1  - Guntas, Gulcan
A1  - Rajendran, Ranjithkumar
A1  - Shityakov, Sergey
A1  - Höring, Marcus
A1  - Liebisch, Gerhard
A1  - Kosanovic, Djuro
A1  - Ergün, Süleyman
A1  - Nagai, Michiaki
A1  - Förster, Carola Y.
T1  - Quantitative lipidomic analysis of Takotsubo syndrome patients' serum
JF  - Frontiers in Cardiovascular Medicine
N2  - Takotsubo syndrome (TTS), also known as the transient left ventricular apical ballooning syndrome, is in contemporary times known as novel acute cardiac syndrome. It is characterized by transient left ventricular apical akinesis and hyperkinesis of the basal left ventricular portions. Although the precise etiology of TTS is unknown, events like the sudden release of stress hormones, such as the catecholamines and the increased inflammatory status might be plausible causes leading to the cardiovascular pathologies. Recent studies have highlighted that an imbalance in lipid accumulation might promote a deviant immune response as observed in TTS. However, there is no information on comprehensive profiling of serum lipids of TTS patients. Therefore, we investigated a detailed quantitative lipid analysis of TTS patients using ES-MSI. Our results showed significant differences in the majority of lipid species composition in the TTS patients compared to the control group. Furthermore, the computational analyses presented was able to link the altered lipids to the pro-inflammatory cytokines and disseminate possible mechanistic pathways involving TNFα and IL-6. Taken together, our study provides an extensive quantitative lipidome of TTS patients, which may provide a valuable Pre-diagnostic tool. This would facilitate the elucidation of the underlying mechanisms of the disease and to prevent the development of TTS in the future.
KW  - TTS
KW  - inflammation
KW  - lipids
KW  - TNF-α
KW  - IL6
KW  - PIK3R1
KW  - NF-kappa-B
KW  - phosphatidylinositol
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270832
SN  - 2297-055X
VL  - 9
IS  - 797154
ER  - 
TY  - JOUR
A1  - Rajendran, Ranjithkumar
A1  - Rajendran, Vinothkumar
A1  - Giraldo-Velasquez, Mario
A1  - Megalofonou, Fevronia-Foivi
A1  - Gurski, Fynn
A1  - Stadelmann, Christine
A1  - Karnati, Srikanth
A1  - Berghoff, Martin
T1  - Oligodendrocyte-specific deletion of FGFR1 reduces cerebellar inflammation and neurodegeneration in MOG\(_{35-55}\)-induced EAE
JF  - International Journal of Molecular Sciences
N2  - 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 (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.
KW  - FGFR1
KW  - oligodendrocytes
KW  - demyelination
KW  - inflammation
KW  - cerebellum
KW  - EAE
KW  - MS
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284296
SN  - 1422-0067
VL  - 22
IS  - 17
ER  -